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Dabrosin, Charlotta
Publications (10 of 51) Show all publications
Vazquez Rodriguez, G., Abrahamsson, A., Jensen, L. D. & Dabrosin, C. (2018). Adipocytes Promote Early Steps of Breast Cancer Cell Dissemination via Interleukin-8. Frontiers in Immunology, 9, 1-17, Article ID 1767.
Open this publication in new window or tab >>Adipocytes Promote Early Steps of Breast Cancer Cell Dissemination via Interleukin-8
2018 (English)In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 9, p. 1-17, article id 1767Article in journal (Refereed) Published
Abstract [en]

Fat is a major tissue component in human breast cancer (BC). Whether breast adipocytes (BAd) affect early stages of BC metastasis is yet unknown. BC progression is dependent on angiogenesis and inflammation, and interleukin-8 (IL-8) and vascular endothelial growth factor (VEGF) are key regulators of these events. Here, we show that BAd increased the dissemination of estrogen receptor positive BC cells (BCC) in vivo in the zebrafish model of metastasis, while dissemination of the more aggressive and metastatic BCC such as estrogen receptor negative was unaffected. While anti-VEGF and anti-IL-8 exhibited equal inhibition of angiogenesis at the primary tumor site, anti-IL-8 reduced BCC dissemination whereas anti-VEGF had minor effects on this early metastatic event. Mechanistically, overexpression of cell-adhesion molecules in BCC and neutrophils via IL-8 increased the dissemination of BCC. Importantly, the extracellular in vivo levels of IL-8 were 40-fold higher than those of VEGF in human BC. Our results suggest that IL-8 is a clinical relevant and promising therapeutic target for human BC.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2018
Keywords
breast cancer, microdialysis, zebrafish, angiogenesis, inflammation
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-150059 (URN)10.3389/fimmu.2018.01767 (DOI)000440193400002 ()
Funder
Swedish Cancer Society, 2015/309Swedish Research Council, 2013-2457
Available from: 2018-08-08 Created: 2018-08-08 Last updated: 2018-08-30
Vazquez Rodriguez, G., Abrahamsson, A., Jensen, L. & Dabrosin, C. (2017). Estradiol promotes breast cancer cell migration via recruitment and activation of neutrophils. Cancer Immunology research, 5(3), 234-247, Article ID 28159748.
Open this publication in new window or tab >>Estradiol promotes breast cancer cell migration via recruitment and activation of neutrophils
2017 (English)In: Cancer Immunology research, ISSN 2326-6066, Vol. 5, no 3, p. 234-247, article id 28159748Article in journal (Refereed) Published
Abstract [en]

Estradiol (E2) plays a key role in breast cancer progression. Most breast cancer recurrences express the estrogen receptor (ER), but nearly 50% of patients are resistant to antiestrogen therapy. Novel therapeutic targets of ER-positive breast cancers are needed. Protumoral neutrophils expressing the lymphocyte function-associated antigen 1 (LFA-1) integrin may mediate cancer metastasis, and TGFβ1 is the major chemoattractant for neutrophils. The role of E2 in neutrophil–ER+ breast cancer cell interactions is unknown. We studied this in vivo using murine breast cancers in immunocompetent mice and human breast cancers in nude mice. Cell dissemination was evaluated in a zebrafish model, and microdialysis of breast cancer patients was performed. In vitro studies were done with mammosphere cultures of breast cancer cells and human neutrophils. We found that E2 increased the number of LFA-1+ neutrophils recruited to the invasive edge of mouse tumors, increased TGFβ1 secretion and promoted neutrophil infiltration in mammospheres, and induced overexpression of LFA-1 in neutrophils. In zebrafish, in the presence of E2, neutrophils increased dissemination of ER+ breast cancer cells via LFA-1 and TGFβ1, thus causing noninvasive cancer cells to be highly metastatic. Time-lapse imaging in zebrafish revealed close interactions of neutrophils with cancer cells, which drove breast cancer metastasis. We also found that extracellular TGFβ1 was overproduced in human breast cancer tissue compared with adjacent normal breast tissue. Thus, E2 can regulate immune/cancer cell interactions in tumor microenvironments. Our results indicate that extracellular TGFβ1 is a relevant target in human breast cancer.

Place, publisher, year, edition, pages
American Association for Cancer Research, 2017
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-135330 (URN)10.1158/2326-6066.CIR-16-0150 (DOI)000396023000006 ()28159748 (PubMedID)
Funder
Swedish Cancer Society, 2015/309Swedish Research Council, 2013-2457Linköpings universitet
Note

Funding agencies: Swedish Cancer Society [2015/309]; Swedish Research Council [2013-2457]; LiU-Cancer; Research Funds of Linkoping University Hospital

Available from: 2017-03-13 Created: 2017-03-13 Last updated: 2018-05-02
Abrahamsson, A., Rzepecka, A. & Dabrosin, C. (2017). Increased nutrient availability in dense breast tissue of postmenopausal women in vivo. Scientific Reports, 7, Article ID 42733.
Open this publication in new window or tab >>Increased nutrient availability in dense breast tissue of postmenopausal women in vivo
2017 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 42733Article in journal (Refereed) Published
Abstract [en]

Metabolic reprogramming is a hallmark of cancer. Nutrient availability in the tissue microenvironment determines cellular events and may play a role in breast carcinogenesis. High mammographic density is an independent risk factor for breast cancer. Whether nutrient availability differs in normal breast tissues with various densities is unknown. Therefore we investigated whether breast tissues with various densities exhibited differences in nutrient availability. Healthy postmenopausal women from the regular mammographic screening program who had either predominantly fatty breast tissue (nondense), n = 18, or extremely dense breast tissue (dense), n = 20, were included. Microdialysis was performed for the in vivo sampling of amino acids (AAs), analyzed by ultra-high performance liquid chromatography with tandem mass spectroscopy, glucose, lactate and vascular endothelial growth factor (VEGF) in breast tissues and, as a control, in abdominal subcutaneous (s.c.) fat. We found that dense breast tissue exhibited significantly increased levels of 20 proteinogenic AAs and that 18 of these AAs correlated significantly with VEGF. No differences were found in the s.c. fat, except for one AA, suggesting tissue-specific alterations in the breast. Glucose and lactate were unaltered. Our findings provide novel insights into the biology of dense breast tissue that may be explored for breast cancer prevention strategies.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2017
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-135389 (URN)10.1038/srep42733 (DOI)000394294800001 ()28198437 (PubMedID)
Note

Funding Agencies|Swedish Cancer Society [2015/309]; Swedish Research Council [2013-2457]; LiU-Cancer; Linkoping University Hospital

Available from: 2017-03-14 Created: 2017-03-14 Last updated: 2018-05-02
Morad, V., Abrahamsson, A., Kjölhede, P. & Dabrosin, C. (2016). Adipokines and Vascular Endothelial Growth Factor in Normal Human Breast Tissue in Vivo - Correlations and Attenuation by Dietary Flaxseed. Journal of mammary gland biology and neoplasia, 21(1-2), 69-76
Open this publication in new window or tab >>Adipokines and Vascular Endothelial Growth Factor in Normal Human Breast Tissue in Vivo - Correlations and Attenuation by Dietary Flaxseed
2016 (English)In: Journal of mammary gland biology and neoplasia, ISSN 1083-3021, E-ISSN 1573-7039, Vol. 21, no 1-2, p. 69-76Article in journal (Refereed) Published
Abstract [en]

Exposure to sex steroids increases the risk of breast cancer but the exact mechanisms are yet to be elucidated. Events in the microenvironment are important for carcinogenesis. Diet containing phytoestrogens can affect the breast microenvironment and alter the risk of breast cancer. It has previously been shown that estrogen regulates extracellular levels of leptin, adiponectin, and VEGF in normal breast tissue in vivo. Whether these proteins correlate in breast tissue in vivo or if diet addition of flaxseed, a major source of phytoestrogens in Western diets, alters adipokine levels in breast tissue are unknown. We used microdialysis to sample proteins of normal human breast tissue and abdominal subcutaneous fat in situ in 34 pre-and postmenopausal women. In vitro, co-culture of breast cancer cells and primary human adipocytes was used. In vivo, in normal breast tissue, a significant positive correlation between VEGF and leptin was detected. No correlations were found in fat tissue. Co-culture of adipocytes and breast cancer cells per se increased the secretion of VEGF and leptin and enhanced the effects of estradiol compared to culture of either cell type alone. In vitro, inhibition of VEGF diminished the release of leptin while inhibition of leptin had no influence on VEGF secretion. The levels of leptin decreased and adiponectin increased after a dietary addition of 25 g of flaxseed/day for one menstrual cycle. We conclude that VEGF and leptin correlate significantly in normal human breast tissue in vivo and that dietary addition of flaxseed affect adipokine levels in the breast.

Place, publisher, year, edition, pages
SPRINGER/PLENUM PUBLISHERS, 2016
Keywords
Flaxseed; Diet; Microdialysis; Estrogen; Leptin; Adiponectin
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-130433 (URN)10.1007/s10911-016-9352-9 (DOI)000379327000009 ()27059487 (PubMedID)
Available from: 2016-08-07 Created: 2016-08-05 Last updated: 2019-06-28
Dabrosin, C. (2015). An overview of pregnancy and fertility issues in breast cancer patients. Annals of Medicine, 47(8), 673-678
Open this publication in new window or tab >>An overview of pregnancy and fertility issues in breast cancer patients
2015 (English)In: Annals of Medicine, ISSN 0785-3890, E-ISSN 1365-2060, Vol. 47, no 8, p. 673-678Article, review/survey (Refereed) Published
Abstract [en]

Breast cancer is one of the most common malignancies of women in the reproductive years. In the Western world there is a trend towards delaying pregnancy to later in life, and in combination with an increased incidence of breast cancer an increased number of women are diagnosed with breast cancer before they have completed their reproductive plans. In addition, breast cancer during pregnancy may affect an increased number of women as the childbearing years are delayed. The survival rate after breast cancer has improved during the last decades, and many young breast cancer survivors will consider a pregnancy subsequent to the completion of adjuvant breast cancer therapy. Traditionally, many women are advised against a pregnancy due to a fear of increased risk of recurrence, especially women with estrogen receptor-positive breast cancer. Due to feasibility issues, evidence from large prospective randomized trials is missing regarding the safety of pregnancy after breast cancer. Today guidelines are based on cohort studies and population-based registry evidence with its limitations. Overall, data suggest that pregnancy after breast cancer therapy is safe, and the current evidence is summarized in this overview.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD, 2015
Keywords
Breast cancer; estrogen receptor; fertility; mammary cancer; pregnancy
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-123841 (URN)10.3109/07853890.2015.1096953 (DOI)000366590600005 ()26542739 (PubMedID)
Available from: 2016-01-11 Created: 2016-01-11 Last updated: 2017-12-01
Wang, Z., Dabrosin, C., Yin, X., Fuster, M. M., Arreola, A., Rathmell, W. K., . . . Jensen, L. D. (2015). Broad targeting of angiogenesis for cancer prevention and therapy. Seminars in Cancer Biology, S1044-579X(15), 00002-00004
Open this publication in new window or tab >>Broad targeting of angiogenesis for cancer prevention and therapy
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2015 (English)In: Seminars in Cancer Biology, ISSN 1044-579X, E-ISSN 1096-3650, Vol. S1044-579X, no 15, p. 00002-00004Article, review/survey (Refereed) Published
Abstract [en]

Deregulation of angiogenesis - the growth of new blood vessels from an existing vasculature - is a main driving force in many severe human diseases including cancer. As such, tumor angiogenesis is important for delivering oxygen and nutrients to growing tumors, and therefore considered an essential pathologic feature of cancer, while also playing a key role in enabling other aspects of tumor pathology such as metabolic deregulation and tumor dissemination/metastasis. Recently, inhibition of tumor angiogenesis has become a clinical anti-cancer strategy in line with chemotherapy, radiotherapy and surgery, which underscore the critical importance of the angiogenic switch during early tumor development. Unfortunately the clinically approved anti-angiogenic drugs in use today are only effective in a subset of the patients, and many who initially respond develop resistance over time. Also, some of the anti-angiogenic drugs are toxic and it would be of great importance to identify alternative compounds, which could overcome these drawbacks and limitations of the currently available therapy. Finding "the most important target" may, however, prove a very challenging approach as the tumor environment is highly diverse, consisting of many different cell types, all of which may contribute to tumor angiogenesis. Furthermore, the tumor cells themselves are genetically unstable, leading to a progressive increase in the number of different angiogenic factors produced as the cancer progresses to advanced stages. As an alternative approach to targeted therapy, options to broadly interfere with angiogenic signals by a mixture of non-toxic natural compound with pleiotropic actions were viewed by this team as an opportunity to develop a complementary anti-angiogenesis treatment option. As a part of the "Halifax Project" within the "Getting to know cancer" framework, we have here, based on a thorough review of the literature, identified 10 important aspects of tumor angiogenesis and the pathological tumor vasculature which would be well suited as targets for anti-angiogenic therapy: (1) endothelial cell migration/tip cell formation, (2) structural abnormalities of tumor vessels, (3) hypoxia, (4) lymphangiogenesis, (5) elevated interstitial fluid pressure, (6) poor perfusion, (7) disrupted circadian rhythms, (8) tumor promoting inflammation, (9) tumor promoting fibroblasts and (10) tumor cell metabolism/acidosis. Following this analysis, we scrutinized the available literature on broadly acting anti-angiogenic natural products, with a focus on finding qualitative information on phytochemicals which could inhibit these targets and came up with 10 prototypical phytochemical compounds: (1) oleic acid, (2) tripterine, (3) silibinin, (4) curcumin, (5) epigallocatechin-gallate, (6) kaempferol, (7) melatonin, (8) enterolactone, (9) withaferin A and (10) resveratrol. We suggest that these plant-derived compounds could be combined to constitute a broader acting and more effective inhibitory cocktail at doses that would not be likely to cause excessive toxicity. All the targets and phytochemical approaches were further cross-validated against their effects on other essential tumorigenic pathways (based on the "hallmarks" of cancer) in order to discover possible synergies or potentially harmful interactions, and were found to generally also have positive involvement in/effects on these other aspects of tumor biology. The aim is that this discussion could lead to the selection of combinations of such anti-angiogenic compounds which could be used in potent anti-tumor cocktails, for enhanced therapeutic efficacy, reduced toxicity and circumvention of single-agent anti-angiogenic resistance, as well as for possible use in primary or secondary cancer prevention strategies.

Place, publisher, year, edition, pages
Elsevier, 2015
Keywords
Angiogenesis Cancer Phytochemicals Treatment Anti-angiogenic
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-115783 (URN)10.1016/j.semcancer.2015.01.001 (DOI)000366619400011 ()25600295 (PubMedID)
Note

Funding agencies: Swedish Society for Medical Research; Goesta Fraenkel Foundation; Ake Wibergs Foundation; Ollie och Elof Ericssons Foundation; Karolinska Institute; Linkoping University; University of Glasgow; Beatson Oncology Center Fund; Cancer Research UK grant

Available from: 2015-03-19 Created: 2015-03-19 Last updated: 2018-04-23
Svensson, S., Abrahamsson, A., Vazquez Rodriguez, G., Olsson, A.-K., Jensen, L., Cao, Y. & Dabrosin, C. (2015). CCL2 and CCL5 Are Novel Therapeutic Targets for Estrogen-Dependent Breast Cancer. Clinical Cancer Research, 21(16), 3794-3805
Open this publication in new window or tab >>CCL2 and CCL5 Are Novel Therapeutic Targets for Estrogen-Dependent Breast Cancer
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2015 (English)In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 21, no 16, p. 3794-3805Article in journal (Refereed) Published
Abstract [en]

Purpose: Novel therapeutic targets of estrogen receptor (ER)-positive breast cancers are urgently needed because current antiestrogen therapy causes severe adverse effects, nearly 50% of patients are intrinsically resistant, and the majority of recurrences have maintained ER expression. We investigated the role of estrogen-dependent chemokine expression and subsequent cancer growth in human tissues and experimental breast cancer models. Experimental Design: For in vivo sampling of human chemokines, microdialysis was used in breast cancers of women or normal human breast tissue before and after tamoxifen therapy. Estrogen exposure and targeted therapies were assessed in immune competent PyMT murine breast cancer, orthotopic human breast cancers in nude mice, cell culture of cancer cells, and freshly isolated human macrophages. Cancer cell dissemination was investigated using zebrafish. Results: ER+ cancers in women produced high levels of extracellular CCL2 and CCL5 in vivo, which was associated with infiltration of tumor-associated macrophages. In experimental breast cancer, estradiol enhanced macrophage influx and angiogenesis through increased release of CCL2, CCL5, and vascular endothelial growth factor. These effects were inhibited by anti-CCL2 or anti-CCL5 therapy, which resulted in potent inhibition of cancer growth. In addition, estradiol induced a protumorigenic activation of the macrophages. In a zebrafish model, macrophages increased cancer cell dissemination via CCL2 and CCL5 in the presence of estradiol, which was inhibited with anti-CCL2 and anti-CCL5 treatment. Conclusions: Our findings shed new light on the mechanisms underlying the progression of ER+ breast cancer and indicate the potential of novel therapies targeting CCL2 and CCL5 pathways. (C)2015 AACR.

Place, publisher, year, edition, pages
AMER ASSOC CANCER RESEARCH, 2015
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-122122 (URN)10.1158/1078-0432.CCR-15-0204 (DOI)000361909100027 ()25901081 (PubMedID)
Note

Funding Agencies|Swedish Cancer Society [2009/799]; Swedish Research Council [2010-3458]; LiU-Cancer; Linkoping University Hospital

Available from: 2015-10-19 Created: 2015-10-19 Last updated: 2018-08-08
Morad, V., Abrahamsson, A., Kjölhede, P. & Dabrosin, C. (2015). Correlation between vascular endothelial growth factor and leptin in normal human breast tissue in vivo.
Open this publication in new window or tab >>Correlation between vascular endothelial growth factor and leptin in normal human breast tissue in vivo
2015 (English)Manuscript (preprint) (Other academic)
Abstract [en]

Introduction: Events in the microenvironment are important for carcinogenesis of the breast. Adipocytes, which produce adipokines with paracrine effects, are the most abundant cell type in breast tissue. Exposure to sex steroids affects the risk of breast cancer. It has previously been shown that estrogen regulates the extracellular levels of leptin, adiponectin, IL-1β, and VEGF in normal human breast tissue in vivo.

Objective: We aimed to determine if there were any relationships between leptin, adiponectin, IL-1β, and/or VEGF in normal human breast tissue in vivo and to elucidate the role of adipocytes in the regulation of these factors.

Design and methods: Microdialysis was used to sample proteins of normal human breast tissue and abdominal subcutaneous (s.c.) fat in situ in pre-and postmenopausal women. An in vitro co-culture model of breast cancer cells and primary mature human adipocytes was used.

Results: In vivo, in normal breast tissue, significant positive correlations between VEGF and leptin, and VEGF and leptin/adiponectin ratio were detected. No correlations were found in s.c. abdominal fat tissue. Co-culture of adipocytes and breast cancer cells per se increased the secretion of VEGF and leptin and enhanced the effects of estradiol compared to culture of either cell type alone. In vitro, inhibition of VEGF diminished the release of leptin while inhibition of leptin had no influence on VEGF secretion. In breast tissue, significant correlations between IL-1β and leptin and VEGF were revealed.

Conclusions: Our results suggest that VEGF regulates leptin in normal human breast tissue. Moreover, physical contact between adipocytes and breast cancer cells, induces phenotypic changes and enhances the effects of estradiol. These mechanisms may be involved in breast cancer progression.

National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-117982 (URN)
Available from: 2015-05-19 Created: 2015-05-19 Last updated: 2019-06-28Bibliographically approved
Block, K. I., Gyllenhaal, C., Lowe, L., Amedei, A., Ruhul Amin, A. R., Amin, A., . . . Zollo, M. (2015). Designing a broad-spectrum integrative approach for cancer prevention and treatment. Seminars in Cancer Biology, 35, S276-S304
Open this publication in new window or tab >>Designing a broad-spectrum integrative approach for cancer prevention and treatment
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2015 (English)In: Seminars in Cancer Biology, ISSN 1044-579X, E-ISSN 1096-3650, Vol. 35, p. S276-S304Article, review/survey (Refereed) Published
Abstract [en]

Targeted therapies and the consequent adoption of "personalized" oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity "broadspectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspects of relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a wide range of high-priority targets (74 in total) that could be modified to improve patient outcomes. For these targets, corresponding low-toxicity therapeutic approaches were then suggested, many of which were phytochemicals. Proposed actions on each target and all of the approaches were further reviewed for known effects on other hallmark areas and the tumor microenvironment Potential contrary or procarcinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixed evidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of the relationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. This novel approach has potential to be relatively inexpensive, it should help us address stages and types of cancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for future research is offered. (C) 2015 The Authors. Published by Elsevier Ltd.

Place, publisher, year, edition, pages
Academic Press, 2015
Keywords
Multi-targeted; Cancer hallmarks; Phytochemicals; Targeted therapy; Integrative medicine
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-123767 (URN)10.1016/j.semcancer.2015.09.007 (DOI)000366619400013 ()26590477 (PubMedID)
Note

Funding Agencies|Terry Fox Foundation Grant [TF-13-20]; UAEU Program for Advanced Research (UPAR) [31S118]; NIH [AR47901, R21CA188818, R15 CA137499-01, F32CA177139, P20RR016477, P20GM103434, R01CA170378, U54CA149145, U54CA143907, R01-HL107652, R01CA166348, R01GM071725, R01 CA109335-04A1, 109511R01CA151304CA168997 A11106131R03CA1711326 1P01AT003961RO1 CA100816P01AG034906 R01AG020642P01AG034906-01A1R01HL108006]; NIH NRSA Grant [F31CA154080]; NIH (NIAID) R01: Combination therapies for chronic HBV, liver disease, and cancer [AI076535]; Sky Foundation Inc. Michigan; University of Glasgow; Beatson Oncology Centre Fund; Spanish Ministry of Economy and Competitivity, ISCIII [PI12/00137, RTICC: RD12/0036/0028]; FEDER from Regional Development European Funds (European Union), Consejeria de Ciencia e Innovacion [CTS-6844, CTS-1848]; Consejeria de Salud of the Junta de Andalucia [PI-0135-2010, PI-0306-2012]; ISCIII [PIE13/0004]; FEDER funds; United Soybean Board; NIH NCCAM Grant [K01AT007324]; NIH NCI Grant [R33 CA161873-02]; Michael Cuccione Childhood Cancer Foundation Graduate Studentship; Ovarian and Prostate Cancer Research Trust, UK; West Virginia Higher Education Policy Commission/Division of Science Research; National Institutes of Health; Italian Association for Cancer Research (AIRC) [IG10636, 15403]; GRACE Charity, UK; Breast Cancer Campaign, UK; Michael Cuccione Childhood Cancer Foundation Postdoctoral Fellowship; Connecticut State University; Swedish Research Council; Swedish Research Society; University of Texas Health Science Centre at Tyler, Elsa U. Pardee Foundation; CPRIT; Cancer Prevention and Research Institute of Texas; NIH National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); NIH National Institute on Alcohol Abuse and Alcoholism (NIAAA); Gilead and Shire Pharmaceuticals; NIH/NCI [1R01CA20009, 5R01CAl27258-05, R21CA184788, NIH P30 CA22453, NCI RO1 28704]; Scottish Governments Rural and Environment Science and Analytical Services Division; National Research Foundation; United Arab Emirates University; Terry Fox Foundation; Novartis Pharmaceutical; Aveo Pharmaceutical; Roche; Bristol Myers Squibb; Bayer Pharmaceutical; Pfizer; Kyowa Kirin; NIH/NIAID Grant [A1076535]; Auckland Cancer Society; Cancer Society of New Zealand; NIH Public Service Grant from the National Cancer Institute [CA164095]; Medical Research Council CCU-Program Grant on cancer metabolism; EU Marie Curie Reintegration Grant [MC-CIG-303514]; Greek National funds through the Operational Program Educational and Lifelong Learning of the National Strategic Reference Framework (NSRF)-Research Funding Program THALES [MIS 379346]; COST Action CM1201 `Biomimetic Radical Chemistry; Duke University Molecular Cancer Biology T32 Training Grant; National Sciences Engineering and Research Council Undergraduate Student Research Award in Canada; Charles University in Prague projects [UNCE 204015, PRVOUK P31/2012]; Czech Science Foundation projects [15-03834Y, P301/12/1686]; Czech Health Research Council AZV project [15-32432A]; Internal Grant Agency of the Ministry of Health of the Czech Republic project [NT13663-3/2012]; National Institute of Aging [P30AG028716-01]; NIH/NCI training grants to Duke University [T32-CA059365-19, 5T32-CA059365]; Ministry of Education, Culture, Sports, Science and Technology, Japan [24590493]; Ministry of Health and Welfare [CCMP101-RD-031, CCMP102-RD-112]; Tzu-Chi University of Taiwan [61040055-10]; Svenska Sallskapet for Medicinsk Forskning; Cancer Research Wales; Albert Hung Foundation; Fong Family Foundation; Welsh Government A4B scheme; NIH NCI; University of Glasgow, Beatson Oncology Centre Fund, CRUK [C301/A14762]; NIH Intramural Research Program; National Science Foundation; American Cancer Society; National Cancer Center [NCC-1310430-2]; National Research Foundation [NRF-2005-0093837]; Sol Goldman Pancreatic Cancer Research Fund Grant [80028595]; Lustgarten Fund Grant [90049125, NIHR21CA169757]; Alma Toorock Memorial for Cancer Research; National Research Foundation of Korea (NRF); Ministry of Science, ICT & Future Planning (MSIP), Republic of Korea [2011-0017639, 2011-0030001]; Ministry of Education of Taiwan [TMUTOP103005-4]; International Life Sciences Institute; United States Public Health Services Grants [NIH R01CA156776]; VA-BLR&D Merit Review Grant [5101-BX001517-02]; V Foundation; Pancreatic Cancer Action Network; Damon Runyon Cancer Research Foundation; Childrens Cancer Institute Australia; University Roma Tre; Italian Association for Cancer Research (AIRC-Grant) [IG15221]; Carlos III Health Institute; Feder funds [AM: CP10/00539, PI13/02277]; Basque Foundation for Science (IKERBASQUE); Marie Curie CIG Grant [2012/712404]; Canadian Institutes of Health Research; Avon Foundation for Women [OBC-134038]; Canadian Institutes of Health [MSH-136647, MOP 64308]; Bayer Healthcare System G4T (Grants4Targets); NIH NIDDK; NIH NIAAA; Shire Pharmaceuticals; Harvard-MIT Health Sciences and Technology Research Assistantship Award; Italian Ministry of University; University of Italy; Auckland Cancer Society Research Centre (ACSRC); German Federal Ministry of Education and Research (Bundesministerium fur Bildung und Forschung, BMBF) [16SV5536K]; European Commission [FP7 259679 "IDEAL"]; Cinque per Mille dellIRPEF-Finanziamento della Ricerca Sanitaria; European Union Seventh Framework Programme (FP7) [278570]; AIRC [10216, 13837]; European Communitys Seventh Framework Program FP7 [311876]; Canadian Institute for Health Research [MOP114962, MOP125857]; Fonds de Recherche Quebec Sante [22624]; Terry Fox Research Institute [1030]; FEDER; MICINN [SAF2012-32810]; Junta de Castilla y Leon [BIO/SA06/13]; ARIMMORA project [FP7-ENV-2011]; European Union; NIH NIDDK [K01DK077137, R03DK089130]; NIH NCI grants [R01CA131294, R21 CA155686]; Avon Foundation; Breast Cancer Research Foundation Grant [90047965]; National Institute of Health, NINDS Grant [K08NS083732]; AACR-National Brain Tumor Society Career Development Award for Translational Brain Tumor Research [13-20-23-SIEG]; Department of Science and Technology, New Delhi, India [SR/FT/LS-063/2008]; Yorkshire Cancer Research; Wellcome Trust, UK; Italian Ministry of Economy and Finance Project CAMPUS-QUARC, within program FESR Campania Region; National Cancer Institute [5P01CA073992]; IDEA Award from the Department of Defense [W81XWH-12-1-0515]; Huntsman Cancer Foundation; University of Miami Clinical and Translational Science Institute (CTSI) Pilot Research Grant [CTSI-2013-P03]; SEEDS You Choose Awards; DoD [W81XVVH-11-1-0272, W81XWH-13-1-0182]; Kimmel Translational Science Award [SKF-13-021]; ACS Scholar award [122688-RSG-12-196-01-TBG]; National Cancer Institute, Pancreatic Cancer Action Network, Pew Charitable Trusts; American Diabetes Association; Elsa U. Pardee Foundation; Scientific Research Foundation for the Returned Oversea Scholars, State Education Ministry and Scientific and Technological Innovation Project, Harbin [2012RFLX5011]; United States National Institutes of Health [ES019458]; California Breast Cancer Research Program [17UB-8708]; National Institutes of Health through the RCMI-Center for Environmental Health [G1200MD007581]; NIH/National Heart, Lung, and Blood Institute Training Grant [T32HL098062]; European FP7-TuMIC [HEALTH-F2-2008-201662]; Italian Association for Cancer research (AIRC) Grant IG [11963]; Regione Campania L.R:N.5; European National Funds [PON01-02388/1 2007-2013]

Available from: 2016-01-11 Created: 2016-01-11 Last updated: 2019-01-21Bibliographically approved
Vazquez Rodriguez, G., Abrahamsson, A., Jensen, L. & Dabrosin, C. (2015). Neutrophils Promote Breast Cancer Progression and Metastasis via LFA-1 Integrin. In: : . Paper presented at 7th International conference on Tumor Microenvironment: Progression, Therapy& Prevention Tel Aviv, Israel October 11 -15, 2015. (pp. 139-140). Springer, 8
Open this publication in new window or tab >>Neutrophils Promote Breast Cancer Progression and Metastasis via LFA-1 Integrin
2015 (English)Conference paper, Poster (with or without abstract) (Other academic)
Abstract [en]

Cancer is considered an inflammatory condition where immune cells play an important role in progression and metastasis. Neutrophils may be pro- or antitumorigenic, depending on their phenotype or the number of infiltrating neutrophils in the tumor microenvironment. Massive infiltration of neutrophils in cancer tissue may elicit a cytotoxic effect, leading to tumor regression, whereas a S139 low-grade neutrophil gradient is tumor progressive. Chemokines, cytokines, and growth factors present in the tumor microenvironment, as well as cell-cell interactions mediated by integrins have shown to be determinant steps for cancer cells to break through the endothelial wall and establish metastatic niches. In this work we evaluated the role of lymphocyte functionassociated antigen 1 (LFA-1) integrin in neutrophils-mediated metastasis of estrogen receptor positive breast cancer cells (MCF-7) cells in a tumor xenograft model in zebrafish and in neutrophil infiltration in MCF-7 mammospheres. The metastatic capability of MCF-7 cells was evaluated in presence or absence of human neutrophils and with/without estradiol treatment. Two days old zebrafish embryos were injected into the perivitelline space with labeled MCF-7 cells and human neutrophils, an anti-human LFA-1 antibody (CD11a) was included. We show that estradiol treatment significantly increased the infiltration of neutrophils into MCF-7 mammospheres and this infiltration was significantly reduced by the presence of an anti-human CD11a antibody. Co-injection of MCF-7 cells with neutrophils significantly increased the migration of MCF-7 cells to distant sites in zebrafish and this effect was inhibited by using an anti-human CD11a antibody. We conclude that neutrophils affect the dissemination of breast cancer cells via LFA-1 integrin. Although estradiol increased the number of infiltrating neutrophils into mammospheres exposure to estradiol seemed to have minor effects on the dissemination in the zebrafish.

Place, publisher, year, edition, pages
Springer, 2015
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:liu:diva-136140 (URN)10.1007/s12307-015-0175-9 (DOI)26374343 (PubMedID)
Conference
7th International conference on Tumor Microenvironment: Progression, Therapy& Prevention Tel Aviv, Israel October 11 -15, 2015.
Funder
Swedish Cancer Society, 2015/309Swedish Research Council, 2013-2457Linköpings universitet
Available from: 2017-03-28 Created: 2017-03-28 Last updated: 2018-01-13Bibliographically approved
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