Expression of functional very late antigen-alpha 1, -alpha 2, -alpha 3 and -alpha 6 integrins on Ewing's sarcoma and primitive peripheral neuroectodermal tumour cells and modulation by interferon-gamma and tumour necrosis factor-alpha.
Twelve different human primary and metastatic Ewing's sarcoma (ES) and primitive peripheral neuroectodermal tumour (pPNET) cell lines were examined by fluorocytometric analysis for the expression of alpha 1, alpha 2, alpha 3 and alpha 6 very late antigen (VLA) beta 1-integrins. VLA-alpha 1, was abundantly expressed on all typical ES cell lines and pPNET cell lines, while absent from atypical (large cell) ES cells. VLA-alpha 2 was displayed on some ES and pPNET cell lines. In two different pPNET cell lines, derived from the same patient, VLA-alpha 2 expression was considerably higher on primary cells compared with metastatic cells. VLA-alpha 3 was exclusively expressed on pPNET cell lines. Expression of VLA-alpha 6 was higher on metastatic than on primary ES and pPNET cells. Adhesion assays on purified extracellular matrix (ECM) proteins, using monospecific adhesion-blocking antibodies, disclosed VLA-1 (alpha 1 beta 1) on typical ES cells and pPNET cells, and VLA-2 (alpha 2 beta 1) on atypical ES cells, as dual collagen type IV (COIV)/laminin (LM) binding sites, and VLA-6 (alpha 6 beta 1) as a specific LM binding site. Treatment of typical ES cells and pPNET cells for up to 48 h with recombinant human interferon-gamma (rhIFN gamma) and tumour necrosis factor-alpha (rhTNF alpha) upregulated alpha 1 and beta 1 expression, concomitant with an increase in cell adhesion to COIV and LM. Alternatively, these cytokines downregulated the expression of alpha 2, alpha 6 and beta 1 on atypical ES cells, concomitant with a decrease in the adhesion to COIV and LM. In conclusion, these findings suggest that the difference in repertory of CO and LM integrin receptors on ES cells and pPNET cells reflects tumour status and degree of differentiation. Furthermore, our data indicate that IFN gamma- and TNF alpha-mediated alteration in the level of expression of distinct VLAs on ES and pPNET cells is correlated with changes in the adhesive behaviour of these tumour cells.
van Valen
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Department of Paediatric Haematology and Oncology, Westfälische Wilhelms-University Medical Center, Münster, Germany.
Hanenberg
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Jürgens
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H
D001859:Bone Neoplasms / Q000737:chemistry*; D001932:Brain Neoplasms / Q000737:chemistry*; D002448:Cell Adhesion / Q000187:drug effects; D003094:Collagen; D015536:Down-Regulation; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007797:Laminin; D018242:Neuroectodermal Tumors, Primitive / Q000737:chemistry*; D016029:Receptors, Very Late Antigen / Q000032:analysis* / Q000378:metabolism; D012512:Sarcoma, Ewing / Q000737:chemistry*; D014407:Tumor Cells, Cultured / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation
D007797:Laminin; D016029:Receptors, Very Late Antigen; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D003094:Collagen