Differential effects of CD40 stimulation on normal and neoplastic cell growth.
CD40 is a molecule in the tumor necrosis factor receptor/nerve growth factor receptor (TNFR/NGFR) family that is present on both normal and neoplastic B lineage cells. It is also expressed on carcinoma and melanoma cells and can be augmented with interferon gamma. CD40 stimulation in normal B cells has been demonstrated to promote normal B cell differentiation and growth in vitro. In contrast to these effects, CD40 stimulation by either anti-CD40 antibodies or a recombinant soluble CD40 ligand can inhibit the growth of human breast carcinomas and aggressive histology B lymphomas in vitro and in vivo. This is believed to occur by activation-induced cell death (AICD) in which stimuli that promote the growth of normal cell types inhibit the growth of neoplastic counterparts. This occurs through the induction of apoptosis, necrosis and/or cell cycle arrest. Thus, CD40 stimulation may be of potential clinical use in the treatment of carcinomas and B cell lymphomas. This review shall provide an overview of the various effects of CD40 stimulation on both normal and neoplastic cell types.
Ziebold
J L
JL
NCI-FCRDC, Laboratory of Leukocyte Biology, Frederick, Maryland 21702, USA.
Hixon
J
J
Boyd
A
A
Murphy
W J
WJ
D000230:Adenocarcinoma / Q000378:metabolism / Q000628:therapy; D001943:Breast Neoplasms / Q000378:metabolism* / Q000628:therapy; D019013:CD40 Antigens / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism* / Q000628:therapy; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000628:therapy; D016923:Cell Death; D005260:Female; D006801:Humans; D016393:Lymphoma, B-Cell / Q000378:metabolism* / Q000628:therapy
D019013:CD40 Antigens