Release from apoptosis correlates with tumor progression in the AKR lymphoma

Disturbance of apoptosis is an established factor in tumorigenesis. The rol e of apoptosis in tumor progression is not yet clear. In the present study we compared the tendency to spontaneous apoptosis (and the proliferative ca pacity) of tumor cells derived from primary (PT) and metastatic tumor (MT) cells of several AKR lymphoma variants. Apoptosis-related gene expression w as also compared. Our results indicate that release from apoptosis has a ro le in the tumor progression of this T cell lymphoma. At the cellular level, a markedly lower apoptotic tendency was observed in MT than in PT cells. T he existence of macrophages only in PT also supports the presence of apopto tic cells in local but not in MTs. By contrast, proliferative capacity does not determine tumor aggressiveness in this system. At the molecular level, we found a higher staining intensity for bcl-2 in MT than in PT cells, sug gesting that bcl-2 might be responsible for the reduced apoptosis in MT com pared to PT cells. Evidence for p53 overexpression was found in the MT cell s of one of the variants but in none of the PT. Comparison of Fas receptor, unexpectedly showed an increased expression in MT versus PT cells, possibl y indicating resistance to Fas-induced apoptosis in the MT cells. (C) 2000 Elsevier Science B.V. All rights reserved.