Coexpression of CD40 and CD40L on B lymphoma and carcinoma cells: an autocrine anti-apoptotic role.
To evaluate a possible autocrine role of CD40L, the expression and functional activity of CD40L on NHL and breast carcinoma cell lines were investigated. Using flow cytometry, CD40 was consistently detectable at the surface of all 5 NHL cell lines tested. CD40L expression was detectable at the surface of DAUDI (54%, MFI 47) and BJAB (12%, MFI 32) cell lines, and marginally on the RAJI cell line (7%, MFI 30), while 4 of 5 NHL cell lines (DAUDI, RAJI, BJAB, BL70) had detectable CD40L mRNA. CD40 was expressed on T47D and BT20 breast carcinoma cell lines while CD40L was detectable on T47D (93%, MFI 137) only. Both BT20 and T47D had detectable CD40 mRNA, while CD40L mRNA was detectable only in the T47D cell line. CD40, but not CD40L, was detectable on 6 renal, 1 prostatic and 1 colon carcinoma cell lines. CD40L expressed on tumor cells was functional, as shown by its capacity to decrease drug-induced apoptosis on CD40 expressing NHL and breast carcinoma cell lines, while irradiated CD40L negative cell line (BT20) had no effect. Blocking CD40L antibody abrogated the protective effect of irradiated CD40L positive T47D cell line against drug-induced apoptosis on BL70 cell line, confirming that CD40L is functional in the DAUDI and T47D cell lines. Importantly, blocking CD40L antibody increased drug-induced apoptosis in CD40L positive cell lines but had no effect on the CD40L negative cell lines. CD40L is expressed on CD40 positive B NHL and breast carcinoma cell lines and induces an autocrine antiapoptotic signal when cells are exposed to cytotoxic agents.
Voorzanger-Rousselot
Nathalie
N
Equipe Cytokines et Cancer, Unité INSERM U453, Centre Léon Bérard, 28 rue Laënnec, 69373 LYON cedex 08, France.
Blay
Jean-Yves
JY
D019138:Antibodies, Blocking; D017209:Apoptosis; D019898:Autocrine Communication / Q000502:physiology; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D019013:CD40 Antigens / Q000235:genetics / Q000378:metabolism*; D023201:CD40 Ligand / Q000235:genetics / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000378:metabolism* / Q000473:pathology; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
D019138:Antibodies, Blocking; D019013:CD40 Antigens; D012333:RNA, Messenger; D023201:CD40 Ligand; D020169:Caspases