Bcl-2-mediated inhibition of apoptosis prevents immunogenicity and restores tumorigenicity of spontaneously regressive tumors.
Tumor cell clones from a rat colon carcinoma differ in their tumorigenicity and immunogenicity. The PRO clones give rise to progressive tumors, whereas the REG clones yield tumors that regress in a few weeks through a specific immune response. REG cells were more sensitive than PRO cells to apoptosis triggered by serum withdrawal in vitro. Furthermore, a fraction of REG cells, but no PRO cells, underwent apoptosis in the hours following injection into syngeneic rats. To further analyze the role of apoptosis, we overexpressed the antiapoptotic protein Bcl-2 in REG cells. Unlike parental or fake-transfected REG cells, Bcl-2-overexpressing REG cells resisted serum withdrawal-induced apoptosis, did not undergo apoptosis at 48 h postinjection into naive syngeneic rats, and gave rise to progressive, metastatic, and lethal tumors. Interestingly, REG-bcl2 cells were rejected by syngeneic hosts that had been preimmunized by an injection of parental REG cells, indicating that Bcl-2 overexpression did not alter tumor cell sensitivity to the effector cells of the immune response. Taken together, these observations indicate that tumor cell apoptosis may contribute to immunogenicity.
Department of Biology and Therapy of Cancer, Institut National de la Santé et de la Recherche Médicale, Faculty of Medicine, Dijon, France.
B
B
Bonnotte
N
N
Favre
M
M
Moutet
A
A
Fromentin
E
E
Solary
M
M
Martin
F
F
Martin
D000230:Adenocarcinoma / Q000209:etiology* / Q000276:immunology* / Q000378:metabolism / Q000556:secondary; D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D003110:Colonic Neoplasms / Q000209:etiology* / Q000276:immunology* / Q000378:metabolism; D016895:Culture Media, Serum-Free; D006084:Graft Rejection / Q000276:immunology; D007113:Immunity, Innate; D009365:Neoplasm Regression, Spontaneous / Q000276:immunology*; D009368:Neoplasm Transplantation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D014407:Tumor Cells, Cultured
D016895:Culture Media, Serum-Free; D019253:Proto-Oncogene Proteins c-bcl-2