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Wasteson, Åke
Alternative names
Publications (10 of 15) Show all publications
Dahlström Wester, M., Wasteson, Å. & Lindström, A. (2009). Targeting malignant glioma cells in vitro using platelet-derived growth factor AA-based conjugates. Journal of drug targeting, 1-10
Open this publication in new window or tab >>Targeting malignant glioma cells in vitro using platelet-derived growth factor AA-based conjugates
2009 (English)In: Journal of drug targeting, ISSN 1029-2330, p. 1-10Article in journal (Refereed) Published
Abstract [en]

Glioblastoma multiforme (GBM) is an unusually aggressive brain tumor; it is also highly heterogeneous. Poor prognosis and a median survival of less than 1 year, using conventional treatment, calls for development of new treatment strategies. Overexpression and/or amplification of platelet-derived growth factor alpha receptors (PDGFalphaRs) in GBM might act as potential targets for a novel therapeutic approach. In this study, conjugates based on PDGFAA-ligand and dextran, of different sizes (10 and 40 kDa dextran), were prepared and investigated regarding targeting properties in vitro. Three human malignant glioma cell lines, U343MGa31L, U343MGaCl2:6, and U563MG, were used because of their previously reported differences in receptor expression and behavior. PDGFAA-based 10 kDa dextran iodine-125 radiolabeled conjugates showed the most favorable properties according to results achieved in accumulation, retention, and localization of cell-associated radioactivity. In comparison with dextran-(125)I-tyrosine delivered radioactivity, the PDGFAA-based dextran conjugates confirm the potential of receptor targeting.

Keywords
Conjugate, dextran, glioblastoma multiforme, PDGFAA, PDGF receptors, targeting
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-18470 (URN)10.1080/10611860902718698 (DOI)19255898 (PubMedID)
Available from: 2009-05-28 Created: 2009-05-28 Last updated: 2009-05-28Bibliographically approved
Hallbeck, A.-L., Walz, T. M., Wasteson, Å. & Lindström, A. (2007). Cooperation of endogenous HER-family members in synovial sarcoma cells: stimulation of HER-2/ErbB2 is dependent on EGFR activation.
Open this publication in new window or tab >>Cooperation of endogenous HER-family members in synovial sarcoma cells: stimulation of HER-2/ErbB2 is dependent on EGFR activation
2007 (English)Article in journal (Refereed) Submitted
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-12781 (URN)
Available from: 2007-11-22 Created: 2007-11-22 Last updated: 2009-03-26
Hallbeck, A.-L., Walz, T. M., Briheim, K. & Wasteson, Å. (2005). TGF-alpha and ErbB2 production in synovial joint tissue: increased expression in arthritic joints. Scandinavian Journal of Rheumatology, 34(3), 204-211
Open this publication in new window or tab >>TGF-alpha and ErbB2 production in synovial joint tissue: increased expression in arthritic joints
2005 (English)In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 34, no 3, p. 204-211Article in journal (Refereed) Published
Abstract [en]

Objective: Cell types present in synovial joint tissues and during synovitis are known to produce epidermal growth factor receptor (EGFR)/ErbB-1/HER-1 and the potent EGFR-ligand transforming growth factor-alpha (TGF-) in vitro. Concomitant expression of TGF-, EGFR, and ErbB2 gives a strong proliferative drive in vitro and in vivo. However, the presence of TGF- and members of the EGFR/EGFR-ligand family has not been thoroughly investigated in joint tissue in vivo. We aimed to determine whether TGF-, EGFR, and ErbB2 are present in human synovial joints, especially during rheumatoid arthritis (RA).

Methods: TGF- protein was immunodetected in knee synovial fluid (SF) collected from 23 RA patients, eight patients with other arthritic conditions, two osteoarthritis (OA) patients, and six post-traumatic patients (control). TGF- mRNA and TGF-, ErbB2, EGFR, and CD68 immunoreactivity were detected in knee synovial biopsies (6 RA/2 OA/6 control) using in situ hybridization and immunohistochemistry. TGF- mRNA was determined in SF cells by reverse transcription polymerase chain reaction (RT-PCR) and/or the Northern blot technique.

Results: TGF- protein was found in the synovial membrane (SM) and in the majority of SF samples. TGF- levels were significantly higher (p<0.001) in SF of RA patients than controls, TGF- protein and mRNA were increased and more widespread in SM of RA patients. In addition, white blood cells collected from RA SF expressed TGF- mRNA. Immunoreactivity for ErbB2 was found in SM and was more widespread in RA patients than in controls.

Conclusion: The presence of TGF- in normal SF and SM may indicate a physiological maintenance function. The increased expression of TGF- and ErbB2 in RA SF and SM may give rise to an abnormal growth pattern, contributing to inflammatory synovial hyperplasia.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-12780 (URN)10.1080/03009740510017715 (DOI)
Available from: 2007-11-22 Created: 2007-11-22 Last updated: 2017-12-14
Dahlström Wester, M., Capala, J., Lindström, P., Wasteson, A. & Lindström, A. (2004). Accumulation of boron in human malignant glioma cells in vitro is cell type dependent. Journal of Neuro-Oncology, 68(3), 199-205
Open this publication in new window or tab >>Accumulation of boron in human malignant glioma cells in vitro is cell type dependent
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2004 (English)In: Journal of Neuro-Oncology, ISSN 0167-594X, E-ISSN 1573-7373, Vol. 68, no 3, p. 199-205Article in journal (Refereed) Published
Abstract [en]

It has been shown that human malignant glioma tumours consist of several subpopulations of tumour cells. Due to heterogeneity and different degrees of vascularisation cell subpopulations possess varying resistance to chemo- or radiation therapy. Therefore, therapy is dependent on the ability to specifically target a tumour cell. Boron neutron capture therapy (BNCT) is a bimodal method, in radiation therapy, taking advantage of the ability of the stable isotope boron-10 to capture neutrons. It results in disintegration products depositing large amounts of energy within a short length, approximately one cell diameter. Thereby, selective irradiation of a target cell may be accomplished if a sufficient amount of boron has been accumulated and hence the cell-associated boron concentration is of critical importance. The accumulation of boron, boronophenylalanine (BPA), was investigated in two human glioma cell subpopulations and a human fibroblast cell line in vitro. The cells were incubated at low boron concentrations (0-5 microg B/ml). Oil filtration was then used for separation of extracellular and cell-associated boron. Inductively coupled plasma atomic emission spectroscopy (ICP-AES) was used for boron determination. Significant (P < 0.05) differences in accumulation ratio (relation between cell-associated and extracellular boron concentration) between human malignant glioma cell lines were found. Human fibroblasts, used to represent normal cells, showed a growth-dependent uptake and a lower accumulation ratio than the glioma cells. Our findings indicate that BPA concentration, incubation time and differences in boron uptake between cell subpopulations should be considered in BNCT.

Keywords
BNCT, BPA, fibroblasts, glioblastoma multiforme, glioma cell lines, in vitro
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-18467 (URN)10.1023/B:NEON.0000033489.54011.6b (DOI)15332322 (PubMedID)
Available from: 2009-05-28 Created: 2009-05-28 Last updated: 2017-12-13Bibliographically approved
Hallbeck, A.-L., Walz, T. M. & Wasteson, Å. (2001). Interleukin-6 enhances transforming growth factor-alpha mRNA expression in macrophage-like human monocytoid (U-937-1) cells. Bioscience Reports, 21(3), 325-339
Open this publication in new window or tab >>Interleukin-6 enhances transforming growth factor-alpha mRNA expression in macrophage-like human monocytoid (U-937-1) cells
2001 (English)In: Bioscience Reports, ISSN 0144-8463, Vol. 21, no 3, p. 325-339Article in journal (Refereed) Published
Abstract [en]

We have previously reported that the human monocytoid cell line U-937-1 constitutively expresses transforming growth factor-alpha (TGF-α) and that the steady-state levels of TGF-α mRNA as well as TGF-α protein release increase when U-937-1 cells are differentiated towards monocytes/macrophages. Interleukin-6 (IL-6), which has been shown to have growth-stimulatory effects on a number of cell types, has recently been shown to enhance TGF-α expression in keratinocytes. In the present study we investigated whether TGF-α expression in macrophage-like cells could be regulated by IL-6 using U-937-1 cells as a model system of monocyte/macrophage differentiation.

U-937-1 cells were differentiated with retinoic acid (RA), vitamin D3 (Vit-D3) or phorbol-12-myristate-13-acetate (PMA) for 4 days and were then treated with human recombinant IL-6 (1000 IU/ml) for up to 24 hr. Northern blot analysis revealed that cells differentiated with PMA, inducing the phenotype of a secretory macrophage, markedly increased their TGF-α mRNA levels (2.7-fold) when treated with IL-6; the response was maximal at 6 hr and remained high at 12 hr. The expression of the TGF-α gene was accompanied by release of TGF-α protein into the cell culture medium, irrespective of differentiating agent, as demonstrated by enzyme-linked immunosorbent assay (ELISA), as well as by surface expression of pro-TGF-α as determined by indirect immunofluorescent cytometry. However, the superinduction of the TGF-α gene by IL-6 in cells differentiated with PMA was not accompanied by any increase in TGF-α protein release or pro-TGF-α surface expression.

We conclude that since IL-6 causes increased steady-state levels of TGF-α mRNA in macrophage-like cells, it may prime these cells for production of this growth factor. Furthermore, we have shown that the IL-6 receptor complex is functional in U-937-1 cells induced to differentiate towards a secretory macrophage by treatment with PMA.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-12778 (URN)10.1023/A:1013238300100 (DOI)
Available from: 2007-11-22 Created: 2007-11-22 Last updated: 2009-08-18
Höddelius, P., Lirvall, M., Wasteson, Å., Loitto, V. & Magnusson, K.-E. (2000). Both Intra- and Extracellular Ca2 Participate in the Regulation of the Lateral Diffusion of the PDGF-β2 Receptor. Bioscience Reports, 20(2), 119-127
Open this publication in new window or tab >>Both Intra- and Extracellular Ca2 Participate in the Regulation of the Lateral Diffusion of the PDGF-β2 Receptor
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2000 (English)In: Bioscience Reports, ISSN 0144-8463, E-ISSN 1573-4935, Vol. 20, no 2, p. 119-127Article in journal (Refereed) Published
Abstract [en]

When the receptors for platelet-derived growth factor (PDGF) are activatedthey aggregate, become tyrosine-phosphorylated and elicit a cascade ofdown-stream signals, including mobilization of Ca2+ from intra- andextracellular stores. Receptor mobility in the plane of the membrane isa prerequisite for receptor aggregation and further signalling. Using humanforeskin fibroblasts (AG 1523) and fluorescence recovery afterphotobleaching (FRAP), we therefore assessed the lateral mobilitycharacteristics of PDGF-β2 receptors by their diffusioncoefficient (D), and fraction of mobile receptors (R). This was done oncells stimulated with either normal human serum (NHS) or PDGF underdifferent Ca2+-conditions.

The results suggest that both intra- and extracellular free Ca2+influence the mobility characteristics of the PDGF-β2receptor. Interestingly, the extracellular Ca2+ seems to imposegeneral restrictions on the mobility of receptors, since R increased whenextracellular Ca2+ was quenched with EGTA, whereas intracellularclamping of Ca2+ transients with MABTAM (BAPT/AM) primarily affectedD. When both intra- and extracellular Ca2+ were quenced, D remainedlow and R high, further supporting the proposition that they achievedistinct effects. Inhibition of tyrosine phosphorylation with Erbstatin,partly inhibited the NHS effects and released PDGF-induced receptorimmobilization. Ratio imaging with Fura-2 displayed that both NHS and PDGFinduced changes in intracellular free [Ca2+]. In view of the presentdata it might have important effects on the state of the receptor in themembrane, for instance by regulating its lateral mobility, communicationwith other receptors and signalling functions in the membrane.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-25447 (URN)10.1023/A:1005519501194 (DOI)9893 (Local ID)9893 (Archive number)9893 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
Löfgren, R., Serrander, L., Forsberg, M., Wilsson, Å., Wasteson, Å. & Stendahl, O. (1999). CR3, FcγRIIA and FcγRIIIB induce activation of the respiratory burst in human neutrophils: the role of intracellular Ca2+, phospholipase D and tyrosine phosphorylation. Biochimica et Biophysica Acta. Molecular Cell Research, 1452(1), 46-59
Open this publication in new window or tab >>CR3, FcγRIIA and FcγRIIIB induce activation of the respiratory burst in human neutrophils: the role of intracellular Ca2+, phospholipase D and tyrosine phosphorylation
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1999 (English)In: Biochimica et Biophysica Acta. Molecular Cell Research, ISSN 0167-4889, E-ISSN 1879-2596, Vol. 1452, no 1, p. 46-59Article in journal (Refereed) Published
Abstract [en]

Human neutrophils express two different types of phagocytic receptors, complement receptors (CR) and Fc receptors. In order to characterize the different signaling properties of each receptor we have used non-adherent human neutrophils and investigated CR3, FcγRIIA and FcγRIIIB for their signaling capacity. Selective activation of each receptor was achieved by coupling specific antibodies to heat-killed Staphylococcus aureus particles, Pansorbins, through their Fc moiety. Despite the fact that these particles are not phagocytosed, we show that addition of Pansorbins with anti-CD18 antibodies recognizing CR3 induced prominent signals leading to a respiratory burst. Stimulation with anti-FcγRIIIB Pansorbins induced about half of the response induced by anti-CR3 Pansorbins, whereas anti-FcγRIIA Pansorbins induced an even weaker signal. However, FcγRIIA induced strong phosphorylation of p72syk whereas FcγRIIIB induced only a very weak p72syk phosphorylation. During CR3 stimulation no tyrosine phosphorylation of p72syk was seen. Both phospholipase D and NADPH oxidase activities were dependent on intracellular calcium. This is in contrast to tyrosine phosphorylation of p72syk that occurred even in calcium-depleted cells, indicating that oxygen metabolism does not affect p72syk phosphorylation. Inhibitors of tyrosine phosphorylation blocked the respiratory burst induced by both FcγRIIA and FcγRIIIB as well as CR3. This shows that tyrosine phosphorylation of p72syk is an early signal in the cascade induced by FcγRIIA but not by CR3.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-25448 (URN)10.1016/S0167-4889(99)00112-3 (DOI)9894 (Local ID)9894 (Archive number)9894 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
Abdiu, A., Wingren, S., Larsson, S.-E., Wasteson, Å. & Walz, T. (1999). Effects of human platelet-derived growth factor-AB on sarcoma growth in vitro and in vivo.. Cancer Letters, 141, 39-45
Open this publication in new window or tab >>Effects of human platelet-derived growth factor-AB on sarcoma growth in vitro and in vivo.
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1999 (English)In: Cancer Letters, ISSN 0304-3835, E-ISSN 1872-7980, Vol. 141, p. 39-45Article in journal (Refereed) Published
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-24818 (URN)9216 (Local ID)9216 (Archive number)9216 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13
Abdiu, A., Larsson, S.-E., Wasteson, Å. & Walz, T. (1999). Suramin blocks growth-stimulatory effects of platelet-derived growth factor on malignant fibrous histiocytomas in vitro.. Cancer Letters, 146, 189-194
Open this publication in new window or tab >>Suramin blocks growth-stimulatory effects of platelet-derived growth factor on malignant fibrous histiocytomas in vitro.
1999 (English)In: Cancer Letters, ISSN 0304-3835, E-ISSN 1872-7980, Vol. 146, p. 189-194Article in journal (Refereed) Published
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-24820 (URN)9217 (Local ID)9217 (Archive number)9217 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13
Lirvall, M., Ljungquist-Höddelius, P., Wasteson, Å. & Magnusson, K.-E. (1996). UVB radiation affects the mobility of epidermal growth factor receptors in human keratinocytes and fibroblasts. Bioscience Reports, 16(3), 227-238
Open this publication in new window or tab >>UVB radiation affects the mobility of epidermal growth factor receptors in human keratinocytes and fibroblasts
1996 (English)In: Bioscience Reports, ISSN 0144-8463, E-ISSN 1573-4935, Vol. 16, no 3, p. 227-238Article in journal (Refereed) Published
Abstract [en]

Growth factor receptors transmit biological signals for the stimulation of cell growth in vitro and in vivo and their autocrine stimulation may be involved in tumorigenesis. It is therefore, of great value to understand receptor reactions in response to ultraviolet (UV) light which certain normal human cells are invaribly exposed to during their growth cycle. UV irradiation has recently been shown to deplete antioxidant enzymes in human skin. The aims of the present study were a) to compare the lateral mobility of epidermal growth factor receptors (EGF-R) in cultured human keratinocytes and human foreskin fibroblasts, b) to investigate effects of ultraviolet B radiation on the mobility of EGF-R in these cells, and c) study the response of EGF-R on addition of antioxidant enzymes. The epidermal growth factor receptors were labeled with rhodaminated EGF, the lateral diffusion was determined and the fraction of mobile EGF-R assessed with the fluorescence recovery after photobleaching (FRAP). We found that human keratinocytes display a higher basal level of EGF-R mobility than human skin fibroblasts, viz, with diffusion coefficients (D ± standard error of the mean, SEM) of 4.2 ± 0.2 x 10-10 cm2/s, and 1.8 ± 0.2 x 10-10 cm2/s, respectively. UVB-irradiated fibroblasts showed an almost four-fold increase in the diffusion coefficient; D was 6.3 ± 0.3 x 10-10 cm2/s. The keratinocytes, however, displayed no significant increase in receptor diffusion after irradiation; D was 5.1 ± 0.8 x 10-10 cm2/s. In both cell types the percentage of EGF-R fluorescence recovery after photobleaching, i.e. the fraction of mobile receptors, was significantly increased after irradiation. In keratinocytes it increased from 69% before irradiation to 78% after irradiation. Analogous figures for fibroblasts were 61% and 73%. The effect of UVB on fibroblast receptors was abolished by prior addition of superoxide dismutase (SOD) and catalase (CAT). It is concluded that UVB radiation of fibroblasts and keratinocytes can affect their biophysical properties of EGF-R. The finding that addition of antioxidant enzymes prevented the UVB effect in fibroblasts may indicate the involvement of reactive oxygen metabolites.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-81073 (URN)10.1007/BF01207337 (DOI)
Available from: 2012-09-06 Created: 2012-09-06 Last updated: 2017-12-07Bibliographically approved
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