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Wäster, Petra
Alternative names
Publications (10 of 14) Show all publications
Wäster, P., Eriksson, I., Vainikka, L., Rosdahl, I. & Öllinger, K. (2016). Extracellular vesicles are transferred from melanocytes to keratinocytes after UVA irradiation. Scientific Reports, 6(27890)
Open this publication in new window or tab >>Extracellular vesicles are transferred from melanocytes to keratinocytes after UVA irradiation
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2016 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, no 27890Article in journal (Refereed) Published
Abstract [en]

Ultraviolet (UV) irradiation induces skin pigmentation, which relies on the intercellular crosstalk of melanin between melanocytes to keratinocytes. However, studying the separate effects of UVA and UVB irradiation reveals differences in cellular response. Herein, we show an immediate shedding of extracellular vesicles (EVs) from the plasma membrane when exposing human melanocytes to UVA, but not UVB. The EV-shedding is preceded by UVA-induced plasma membrane damage, which is rapidly repaired by Ca2+-dependent lysosomal exocytosis. Using co-cultures of melanocytes and keratinocytes, we show that EVs are preferably endocytosed by keratinocytes. Importantly, EV-formation is prevented by the inhibition of exocytosis and increased lysosomal pH but is not affected by actin and microtubule inhibitors. Melanosome transfer from melanocytes to keratinocytes is equally stimulated by UVA and UVB and depends on a functional cytoskeleton. In conclusion, we show a novel cell response after UVA irradiation, resulting in transfer of lysosome-derived EVs from melanocytes to keratinocytes.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2016
National Category
Cell Biology
Identifiers
urn:nbn:se:liu:diva-130287 (URN)10.1038/srep27890 (DOI)000378036300001 ()27293048 (PubMedID)
Note

Funding Agencies|Swedish Research Council; Swedish Cancer Society; Welander-Finsen Foundation; County Council of Ostergotland; Stiftelsen Olle Engkvist Byggmastare; Konung Gustav V och Drottning Victorias Frimurarestiftelse; Ostgotaregionens Cancerfond

Available from: 2016-08-01 Created: 2016-07-28 Last updated: 2017-11-28
Bivik Eding, C., Domer, J., Wäster, P., Jerhammar, F., Rosdahl, I. & Öllinger, K. (2015). Melanoma Growth and Progression After Ultraviolet A Irradiation: Impact of Lysosomal Exocytosis and Cathepsin Proteases. Acta Dermato-Venereologica, 95(7), 792-797
Open this publication in new window or tab >>Melanoma Growth and Progression After Ultraviolet A Irradiation: Impact of Lysosomal Exocytosis and Cathepsin Proteases
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2015 (English)In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 95, no 7, p. 792-797Article in journal (Refereed) Published
Abstract [en]

Ultraviolet (UV) irradiation is a risk factor for development of malignant melanoma. UVA-induced lysosomal exocytosis and subsequent cell growth enhancement was studied in malignant melanoma cell lines and human skin melanocytes. UVA irradiation caused plasma membrane damage that was rapidly repaired by calcium-dependent lysosomal exocytosis. Lysosomal content was released into the culture medium directly after irradiation and such conditioned media stimulated the growth of non-irradiated cell cultures. By comparing melanocytes and melanoma cells, it was found that only the melanoma cells spontaneously secreted cathepsins into the surrounding medium. Melanoma cells from a primary tumour showed pronounced invasion ability, which was prevented by addition of inhibitors of cathepsins B, D and L. Proliferation was reduced by cathepsin L inhibition in all melanoma cell lines, but did not affect melanocyte growth. In conclusion, UVA-induced release of cathepsins outside cells may be an important factor that promotes melanoma growth and progression.

Place, publisher, year, edition, pages
ACTA DERMATO-VENEREOLOGICA, 2015
Keywords
lysosome; cathepsin; UVA; exocytosis; melanocyte; melanoma
National Category
Dermatology and Venereal Diseases
Identifiers
urn:nbn:se:liu:diva-122545 (URN)10.2340/00015555-2064 (DOI)000362925500005 ()25669167 (PubMedID)
Note

Funding Agencies|Swedish Research Council; Ostgotaregionens Cancer Foundation; Stiftelsen Olle Engkvist Byggmastare; Swedish Cancer Society; Welander-Finsen Foundation

Available from: 2015-11-06 Created: 2015-11-06 Last updated: 2017-12-01
Wäster, P., Rosdahl, I. & Öllinger, K. (2014). Cell fate regulated by nuclear factor-κB- and activator protein-1-dependent signalling in human melanocytes exposed to ultraviolet A and ultraviolet B.. British Journal of Dermatology, 171(6), 1336-1346
Open this publication in new window or tab >>Cell fate regulated by nuclear factor-κB- and activator protein-1-dependent signalling in human melanocytes exposed to ultraviolet A and ultraviolet B.
2014 (English)In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 171, no 6, p. 1336-1346Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Ultraviolet (UV) radiation constitutes an important risk factor for malignant melanoma, but the wavelength responsible for the initiation of this disease is not fully elucidated. Solar UV induces multiple signalling pathways that are critical for initiation of apoptotic cell death as a cellular defence against malignant transformation.

OBJECTIVES: To evaluate the involvement of the transcription factors nuclear factor (NF)-κB and activator protein (AP)-1 in the signalling pathways induced by UVA or UVB irradiation in human melanocytes.

METHODS: Primary cultures of normal human melanocytes were irradiated with UVA or UVB, and the concomitant DNA damage and redox alterations were monitored. The resulting activation of the NF-κB and AP-1 signalling pathways and subsequent apoptosis were studied.

RESULTS: UVB irradiation causes DNA damage detected as formation of cyclobutane pyrimidine dimers, while UVA induces increased levels of 8-hydroxydeoxyguanosine and lipid peroxidation. UVA and UVB initiate phosphorylation of c-Jun N-terminal protein kinase and extracellular signal-regulated kinase, and the apoptosis signalling pathways converge into a common mechanism. Downregulation of c-Jun suppresses AP-1-mediated signalling and prevents apoptosis upstream of lysosomal and mitochondrial membrane permeabilization, whereas inhibition of NF-κB by SN50 increases apoptosis.

CONCLUSIONS: We conclude that AP-1 induces proapoptotic signalling, whereas NF-κB is a key antiapoptotic/prosurvival factor in both UVA- and UVB-induced cellular damage in human melanocytes, which might in turn impact melanoma development and progression.

Place, publisher, year, edition, pages
John Wiley & Sons, 2014
National Category
Clinical Medicine Basic Medicine
Identifiers
urn:nbn:se:liu:diva-112883 (URN)10.1111/bjd.13278 (DOI)000347236100174 ()25046326 (PubMedID)
Note

Funding text:

This study was supported by the Swedish Research Council, the Swedish Cancer Society, the County Council of Ostergotland, Konung Gustav V och Drottning Victorias Frimurarestiftelse and the Welander-Finsen Foundation.

Available from: 2014-12-18 Created: 2014-12-18 Last updated: 2018-01-11Bibliographically approved
Thunell, L., Bivik, C., Wäster, P., Fredrikson, M., Stjernstrom, A., Synnerstad, I., . . . Enerbäck, C. (2014). MDM2 SNP309 promoter polymorphism confers risk for hereditary melanoma. Melanoma research, 24(3), 190-197
Open this publication in new window or tab >>MDM2 SNP309 promoter polymorphism confers risk for hereditary melanoma
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2014 (English)In: Melanoma research, ISSN 0960-8931, E-ISSN 1473-5636, Vol. 24, no 3, p. 190-197Article in journal (Refereed) Published
Abstract [en]

The p53 pathway regulates stress response, and variations in p53, MDM2, and MDM4 may predispose an individual to tumor development. The aim of this study was to study the impact of genetic variation on sporadic and hereditary melanoma. We have analyzed a combination of three functionally relevant variants of the p53 pathway in 258 individuals with sporadic malignant melanomas, 50 with hereditary malignant melanomas, and 799 healthy controls. Genotyping was performed by PCR-restriction fragment length polymorphism, pyrosequencing, and allelic discrimination. We found an increased risk for hereditary melanoma in MDM2 GG homozygotes, which was more pronounced among women (P=0.035). In the event of pairwise combinations of the single nucleotide polymorphisms, a risk elevation was shown for MDM2 GG homozygotes/p53 wild-type Arg in hereditary melanoma (P=0.01). Individuals with sporadic melanomas of the superficial spreading type, including melanoma in situ, showed a slightly higher frequency of the MDM2 GG genotype compared with those with nodular melanomas (P=0.04). The dysplastic nevus phenotype, present in the majority of our hereditary melanoma cases and also in some sporadic cases, further enhanced the effect of the MDM2 GG genotype on melanoma risk (P=0.005). In conclusion, the results show an association between MDM2 SNP309 and an increased risk for hereditary melanoma, especially among women. Analysis of sporadic melanoma also shows an association between MDM2 and the superficial spreading melanoma subtype, as well as an association with the presence of dysplastic nevi in sporadic melanoma.

Place, publisher, year, edition, pages
Lippincott, Williams andamp; Wilkins, 2014
Keywords
superficial spreading melanoma; MDM2; hereditary melanoma; MDM4; p53; dysplastic nevi
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-107446 (URN)10.1097/CMR.0000000000000063 (DOI)000335683500002 ()
Available from: 2014-06-12 Created: 2014-06-12 Last updated: 2017-12-05
Wäster, P., Eriksson, I., Vainikka, L. & Öllinger, K. (2014). Sunbathing: What’ve lysosomes got to do with it?. Communicative & Integrative Biology, 7(1), e28723-1-e28723-5
Open this publication in new window or tab >>Sunbathing: What’ve lysosomes got to do with it?
2014 (English)In: Communicative & Integrative Biology, ISSN 1942-0889, E-ISSN 1942-0889, Vol. 7, no 1, p. e28723-1-e28723-5Article in journal (Refereed) Published
Abstract [en]

Solar radiation is an important risk factor for skin cancer, the incidence of which is increasing, especially in the fair-skinned populations of the world. While the ultraviolet (UV)B component has direct DNA damaging ability, UVA-induced effects are currently mainly attributed to the production of reactive oxygen species. In our recent study, we compared the effects of UVA and UVB radiation on human keratinocytes and found that UVA-induced plasma membrane damage was rapidly repaired by lysosomal exocytosis, which was detected based on the expression of lysosomal membrane associated protein-1 (LAMP-1) on the plasma membrane of non-permeabilized cells. Later, the keratinocytes died through caspase-8 mediated apoptosis. In contrast, the plasma membranes of keratinocytes exposed to UVB showed no LAMP-1 expression, and, although the cells died by apoptosis, no initial caspase-8 activity was detected. We have also demonstrated the occurrence of UVA-induced lysosomal exocytosis in reconstructed skin and shown the relocation of lysosomes from the center of cells to the vicinity of the plasma membrane. Thus, we suggest that lysosomal exocytosis also occurs in keratinocytes covered by the stratum corneum following exposure to UVA. Our findings provide new insight into the mechanism of UVA-induced skin damage.

Place, publisher, year, edition, pages
Austin, Texas, USA: Landes Biosciences, 2014
Keywords
UV irradiation, keratinocytes, lysosomes, exocytosis, plasma membrane repair, lysosomal, associated membrane protein
National Category
Basic Medicine Cell and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-107147 (URN)10.4161/cib.28723 (DOI)25346791 (PubMedID)2-s2.0-84902664460 (Scopus ID)
Note

Article Addendum to: H Appelqvist, P Waster, I Eriksson, I Rosdahl, K Ollinger. Lysosomal exocytosis and caspase-8-mediated apoptosis in UVA-irradiated keratinocytes. Journal of Cell Science 2013; 126: 5578- 5584. DOI: 10.1242/jcs.130633

Available from: 2014-06-05 Created: 2014-06-05 Last updated: 2018-01-11Bibliographically approved
Appelqvist, H., Wäster, P., Eriksson, I., Rosdahl, I. & Öllinger, K. (2013). Lysosomal exocytosis and caspase-8-mediated apoptosis in UVA-irradiated keratinocytes. Journal of Cell Science, 126(24), 5578-5584
Open this publication in new window or tab >>Lysosomal exocytosis and caspase-8-mediated apoptosis in UVA-irradiated keratinocytes
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2013 (English)In: Journal of Cell Science, ISSN 0021-9533, E-ISSN 1477-9137, Vol. 126, no 24, p. 5578-5584Article in journal (Refereed) Published
Abstract [en]

Ultraviolet (UV) irradiation is a major environmental carcinogen involved in the development of skin cancer. To elucidate the initial signaling during UV-induced damage in human keratinocytes, we investigated lysosomal exocytosis and apoptosis induction. UVA, but not UVB, induced plasma membrane damage, which was repaired by Ca2+-dependent lysosomal exocytosis. The lysosomal exocytosis resulted in extracellular release of cathepsin D and acid sphingomyelinase (aSMase). Two hours after UVA irradiation, we detected activation of caspase-8, which was reduced by addition of anti-aSMAse. Furthermore, caspase-8 activation and apoptosis was reduced by prevention of endocytosis and by the use of cathepsin inhibitors. We conclude that lysosomal exocytosis is part of the keratinocyte response to UVA and is followed by cathepsin-dependent activation of caspase-8. The findings have implications for the understanding of UV-induced skin damage and emphasize that UVA and UVB initiate apoptosis through different signaling pathways in keratinocytes.

Place, publisher, year, edition, pages
Company of Biologists, 2013
Keywords
Keratinocyte; UV irradiation; Lysosome; Cathepsin; Endocytosis; Apoptosis
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-103290 (URN)10.1242/jcs.130633 (DOI)000328686600005 ()
Note

The previous status of this article was manuscript with the title Lysosomal exocytosis repairs the plasma membrane after UVA and is followed by caspase-8 induced apoptosis.

Available from: 2014-01-17 Created: 2014-01-16 Last updated: 2017-08-30
Appelqvist, H., Wäster, P., Kågedal, K. & Öllinger, K. (2013). The lysosome: from waste bag to potential therapeutic target. Journal of Molecular Cell Biology, 5(4), 214-226
Open this publication in new window or tab >>The lysosome: from waste bag to potential therapeutic target
2013 (English)In: Journal of Molecular Cell Biology, ISSN 1674-2788, E-ISSN 1759-4685, Vol. 5, no 4, p. 214-226Article, review/survey (Refereed) Published
Abstract [en]

Lysosomes are ubiquitous membrane-bound intracellular organelles with an acidic interior. They are central for degradation and recycling of macromolecules delivered by endocytosis, phagocytosis, and autophagy. In contrast to the rather simplified view of lysosomes as waste bags, nowadays lysosomes are recognized as advanced organelles involved in many cellular processes and are considered crucial regulators of cell homeostasis. The function of lysosomes is critically dependent on soluble lysosomal hydrolases (e.g. cathepsins) as well as lysosomal membrane proteins (e.g. lysosome-associated membrane proteins). This review focuses on lysosomal involvement in digestion of intra- and extracellular material, plasma membrane repair, cholesterol homeostasis, and cell death. Regulation of lysosomal biogenesis and function via the transcription factor EB (TFEB) will also be discussed. In addition, lysosomal contribution to diseases, including lysosomal storage disorders, neurodegenerative disorders, cancer, and cardiovascular diseases, is presented.

Place, publisher, year, edition, pages
Oxford University Press (OUP): Policy B - Oxford Open Option D, 2013
Keywords
degradation, apoptosis, lysosomal membrane permeabilization, exocytosis, cholesterol
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-97246 (URN)10.1093/jmcb/mjt022 (DOI)000322914000002 ()
Note

Funding Agencies|Swedish Research Council||Swedish Cancer Society||Signhild Engkvist foundation||

Available from: 2013-09-05 Created: 2013-09-05 Last updated: 2017-12-06
Wäster, P., Rosdahl, I., Gilmore, B. F. & Seifert, O. (2011). Ultraviolet exposure of melanoma cells induces fibroblast activation protein-alpha in fibroblasts: Implications for melanoma invasion. International Journal of Oncology, 39(1), 193-202
Open this publication in new window or tab >>Ultraviolet exposure of melanoma cells induces fibroblast activation protein-alpha in fibroblasts: Implications for melanoma invasion
2011 (English)In: International Journal of Oncology, ISSN 1019-6439, Vol. 39, no 1, p. 193-202Article in journal (Refereed) Published
Abstract [en]

Fibroblast activation protein-alpha (FAP-alpha) promotes tumor growth and cell invasiveness through extracellular matrix degradation. How ultraviolet radiation (UVR), the major risk factor for malignant melanoma, influences the expression of FAP-alpha is unknown. We examined the effect of UVR on FAP-alpha expression in melanocytes, keratinocytes and fibroblasts from the skin and in melanoma cells. UVR induces upregulation of FAP-alpha in fibroblasts, melanocytes and primary melanoma cells (PM) whereas keratinocytes and metastatic melanoma cells remained FAP-alpha negative. UVA and UVB stimulated FAP-alpha-driven migration and invasion in fibroblasts, melanocytes and PM. In co-culture systems UVR of melanocytes, PM and cells from regional metastases upregulated FAP-alpha in fibroblasts but only supernatants from non-irradiated PM were able to induce FAP-alpha in fibroblasts. Further, UV-radiated melanocytes and PM significantly increased FAP-alpha expression in fibroblasts through secretory crosstalk via Wnt5a, PDGF-BB and TGF-beta 1. Moreover, UV radiated melanocytes and PM increased collagen I invasion and migration of fibroblasts. The FAP-alpha/DPPIV inhibitor Gly-ProP(OPh)(2) significantly decreased this response implicating FAP-alpha/DPPIV as an important protein complex in cell migration and invasion. These experiments suggest a functional association between UVR and FAP-alpha expression in fibroblasts, melanocytes and melanoma cells implicating that UVR of malignant melanoma converts fibroblasts into FAP-alpha expressing and ECM degrading fibroblasts thus facilitating invasion and migration. The secretory crosstalk between melanoma and tumor surrounding fibroblasts is mediated via PDGF-BB, TGF-beta 1 and Wnt5a and these factors should be evaluated as targets to reduce FAP-alpha activity and prevent early melanoma dissemination.

Place, publisher, year, edition, pages
Spandidos Publications, 2011
Keywords
FAP-alpha; UV irradiation; melanoma; fibroblast; invasion
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-69844 (URN)10.3892/ijo.2011.1002 (DOI)000291504900022 ()
Available from: 2011-08-10 Created: 2011-08-08 Last updated: 2017-12-08Bibliographically approved
Wäster, P. & Öllinger, K. (2009). Redox-Dependent Translocation of p53 to Mitochondria or Nucleus in Human Melanocytes after UVA- and UVB-Induced Apoptosis. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 129(7), 1769-1781
Open this publication in new window or tab >>Redox-Dependent Translocation of p53 to Mitochondria or Nucleus in Human Melanocytes after UVA- and UVB-Induced Apoptosis
2009 (English)In: JOURNAL OF INVESTIGATIVE DERMATOLOGY, ISSN 0022-202X, Vol. 129, no 7, p. 1769-1781Article in journal (Refereed) Published
Abstract [en]

The p53 protein is an important transcription factor and tumor suppressor that is induced in response to many forms of cellular stress. UVA irradiation of human melanocytes caused generation of reactive oxygen species, which altered the intracellular redox balance and was accompanied by translocation of p53 to mitochondria. In contrast, UVB did not affect the redox status and p53 was translocated to the nucleus. Although different intracellular location of p53, UVA/B induced apoptosis through the intrinsic pathway detected as translocation of Bax to mitochondria, release of cytochrome c, and activation of caspases. These events were all prevented by inhibition of p53 with pifithrin-alpha. Furthermore, inhibition of p53 prevented lysosomal membrane permeabilization, detected as translocation of cathepsins to the cytosol, after UVB exposure, whereas UVA-induced lysosomal release was unaffected by inhibition of p53. In control cells, p53 coimmunoprecipitated with the antiapoptotic proteins Bcl-2 and Bcl-x(L) and upon UVA exposure the interaction was replaced by binding to the proapoptotic proteins Bax, Noxa, and Puma. Our findings suggest that UVA-induced apoptosis is caused by extensive oxidative damage leading to p53-regulated mitochondrial release, whereas UVB induces DNA damage and apoptosis signaling upstream of lysosomal membrane permeabilization.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-19662 (URN)10.1038/jid.2008.421 (DOI)
Available from: 2009-07-10 Created: 2009-07-10 Last updated: 2017-08-30
Wäster, P. (2009). UVA/B-induced redox alterations and apoptosis in human melanocytes. Forum for Nordic Dermato-Venerology, 14(1), 26-27
Open this publication in new window or tab >>UVA/B-induced redox alterations and apoptosis in human melanocytes
2009 (English)In: Forum for Nordic Dermato-Venerology, ISSN 1402-2915, Vol. 14, no 1, p. 26-27Article in journal (Other academic) Published
Abstract [en]

[No abstract available]

Place, publisher, year, edition, pages
Uppsala, Sweden: Nordic Dermatology Association, 2009
National Category
Dermatology and Venereal Diseases
Identifiers
urn:nbn:se:liu:diva-18873 (URN)
Available from: 2009-06-05 Created: 2009-06-05 Last updated: 2015-11-11Bibliographically approved
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