EXPRESSION OF FUNCTIONAL VERY LATE ANTIGEN-ALPHA(1), ANTIGEN-ALPHA(2), ANTIGEN-ALPHA(3) AND ANTIGEN-ALPHA(6) INTEGRINS ON EWINGS-SARCOMA AND PRIMITIVE PERIPHERAL NEUROECTODERMAL TUMOR-CELLS AND MODULATION BY INTERFERON-GAMMA AND TUMOR-NECROSIS-FACTOR-ALPHA

Twelve different human primary and metastatic Ewing's sarcoma (ES) and primitive peripheral neuroectodermal tumour (pPNET) cell lines were e xamined by fluorocytometric analysis for the expression of alpha(1), a lpha(2), alpha(3) and alpha(6) very late antigen (VLA) beta(1)-integri ns. VLA-alpha(1), was abundantly expressed on all typical ES cell line s and pPNET cell lines, while absent from atypical (large cell) ES cel ls. 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 m etastatic cells. VLA-alpha(3) was exclusively expressed on pPNET cell lines. Expression of VLA-alpha(6) was higher on metastatic than on pri mary ES and pPNET cells. Adhesion assays on purified extracellular mat rix (ECM) proteins, using monospecific adhesion-blocking antibodies, d isclosed 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 t ype 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 pPNE T cells for up to 48 h with recombinant human interferon-gamma (rhIFN gamma) and tumour necrosis factor-alpha (rhTNF alpha) upregulated alph a(1) and beta(1) expression, concomitant with an increase in cell adhe sion to COIV and LM. Alternatively, these cytokines downregulated the expression of alpha(2), alpha(6) and beta(1) on atypical ES cells, con comitant 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 IF N gamma- and TNF alpha-mediated alteration in the level of expression of distinct VLAs on ES and pPNET cells is correlated with changes in t he adhesive behaviour of these tumour cells.