ANTI-FAS ON NONHEMATOPOIETIC TUMORS - LEVELS OF FAS APO-1 AND BCL-2 ARE NOT PREDICTIVE OF BIOLOGICAL RESPONSIVENESS/

Fas/APO-1 is a cell surface protein known to trigger apoptosis in a va riety of cell types upon specific antibody binding. Although extensive ly studied on normal and malignant hematopoietic cells, little is know n about Fas/APO-1 on nonhematopoietic cells. In the study presented he re, we have examined Fas/APO-1 expression and function on 11 human tum ors of nonhematopoietic origin. By dow cytometric analysis, Fas/APO-1 was expressed on 10 of the 11 tumors at levels comparable to those pre viously reported for lymphoid cells sensitive to the cytolytic effects of anti-Fas. Despite abundant cell surface expression, only 4 of the 10 Fas-positive tumors were sensitive to the cell-killing effects of a nti-Fas. Moreover, anti-Fas enhanced the growth of 2 of 10 Fas-positiv e tumors. Additional studies using cycloheximide demonstrated that de novo protein synthesis was required for anti-Fas-triggered growth stim ulation and, at least in one case, was responsible for the resistance to antibody-induced apoptosis. The biological effects initiated by ant i-Fas engagement, however were not correlated with endogenous bcl-2 ex pression. This report documents that: (a) Fas/APO-1 is widely expresse d on cultured nonhematopoietic tumors; (b) the inherent susceptibility to anti-Fas-induced apoptosis is not correlated with expression of th e Fas/APO-1 protein; (c) Fas/APO-1 engagement can result in growth enh ancement; and (d) protective/growth-promoting proteins other than bcl- 2 may contribute to the diverse spectrum of biological effects induced by anti-Fas engagement of the Fas/APO-1 protein.