Stimulation of CD40 inhibits Fas- or chemotherapy-mediated apoptosis and increases cell motility in human gastric carcinoma cells.
The widespread expression of CD40, a member of the tumor necrosis factor (TNF) receptor (TNFR) superfamily, is likely to account for the central role of CD40 in the regulation of humoral immunity and host defense. Interestingly, the expression of the CD40 in various types of carcinoma cells was often observed and conveys signals regulating diverse cellular responses, ranging from proliferation to growth suppression. Thus, the biologic role of the CD40-CD40L interaction in solid tumors is still controversial. In this study, we investigated the expression and function of the CD40 in gastric carcinoma cells. In 3-4,5 dimethylthiozol-2-yl-2,5-diphenyl tetrazolium bromide (MTT) assay and Annexin V/propidium iodide staining, CD40 stimulation using a soluble form of CD40 ligand did not affect cell viability, but significantly inhibited Fas-mediated or chemotherapy-mediated apoptosis in three CD40-positive gastric cancer cell lines. Moreover, in migration assay, CD40 stimulation induced an elevation of cell motility in CD40-positive gastric carcinoma cells. Our results show that the CD40 expression on gastric carcinoma makes cells less vulnerable to apoptosis induced by Fas or chemotherapy. These results suggest that the CD40 expression on gastric carcinoma may be associated with cell survival and elevation of cell motility.
Yamaguchi
Hiroshi
H
Division of Molecular and Surgical Oncology, Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 874-0838 Beppu, Japan.
Tanaka
Fumiaki
F
Sadanaga
Noriaki
N
Ohta
Mitsuhiko
M
Inoue
Hiroshi
H
Mori
Masaki
M
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis; D019013:CD40 Antigens / Q000378:metabolism*; D023201:CD40 Ligand / Q000378:metabolism; D002166:Camptothecin / Q000494:pharmacology; D002277:Carcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002455:Cell Division; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D002470:Cell Survival; D005434:Flow Cytometry; D006801:Humans; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D019014:fas Receptor / Q000096:biosynthesis / Q000378:metabolism*
D000972:Antineoplastic Agents, Phytogenic; D019013:CD40 Antigens; D013778:Tetrazolium Salts; D013844:Thiazoles; D019014:fas Receptor; D023201:CD40 Ligand; C022616:thiazolyl blue; D002166:Camptothecin