TNF-ALPHA AND ANTI-FAS ANTIBODIES REGULATE LY-6E.1 EXPRESSION BY TUMOR-CELLS - A POSSIBLE LINK BETWEEN ANGIOGENESIS AND LY-6E.1

Angiogenic and poorly angiogenic tumor variants were obtained by an in traperitoneal inoculation of cells from clones of polyoma-virus transf ormed BALB/c 3T3 cells into syngeneic mice. The angiogenic tumor cells expressed a higher tumorigenicity phenotype and a higher capacity to produce artificial pulmonary metastases than cells from the poorly ang iogenic tumors. The former cells expressed also significantly higher l evels of the lymphocyte activation protein Ly-6E.1 than the former cel ls. The two types of cells did not differ in expression levels of CD44 and of a polyoma-virus specific membrane antigen. These results raise the possibility that the angiogenic phenotype is coregulated with Ly- 6. The effect on Ly-6 expression of signal transduction through TNF re ceptors, functioning as pivotal regulators of angiogenesis was therefo re studied. It was found that TNF alpha and more so antibodies against Fas down-regulate expression levels of Ly-6. This down-regulation see med to be selective as expression levels of CD44 were not affected by this treatment. (C) 1996 Elsevier Science B.V.