Suppression of tumor growth by galectin-7 gene transfer.
Galectin-7 is a beta-galactoside-binding animal lectin specifically expressed in stratified epithelia. Its expression is inducible by p53 and is down-regulated in squamous cell carcinomas. Other investigators previously showed that galectin-7 is a proapoptotic protein, and we showed that ectopic expression of galectin-7 in HeLa cells renders the cells more sensitive to a variety of apoptotic stimuli. In the present study, we showed that ectopic expression of galectin-7 in the human colon carcinoma cell line DLD-1 also made the cells more sensitive to apoptosis under various conditions. We also found that galectin-7-transfected DLD-1 (DLD-1-Gal7) cells grew significantly more slowly than control transfectants (DLD-1-V) under normal culture conditions in the absence of apoptosis. Moreover, a significantly lower number of colonies were formed from DLD-1-Gal7 cells than from DLD-1-V cells under anchorage-independent cell growth conditions. Most importantly, tumor formation from DLD-1-Gal7 cells was dramatically reduced compared with DLD-1-V cells when these cells were inoculated s.c. into severe combined immunodeficient mice. DLD-1-Gal7 tumors showed a significantly lower proliferation rate than DLD-1-V tumors as determined by in vivo 5-bromo-2'-deoxyuridine incorporation. DLD-1-Gal7 tumors also contained a lower density of blood vessels than DLD-1-V tumors, suggesting that ectopic expression of galectin-7 suppresses angiogenesis. This may partially account for the greater suppressive effect of galectin-7 on tumor growth in vivo than in vitro. Our results show that galectin-7 has a suppressive effect on tumor growth, suggesting that galectin-7 gene transfer or other means of specifically inducing galectin-7 expression may be a new approach for management of cancers.
Department of Dermatology, University of California, Davis, School of Medicine, Sacramento, California 95817, USA.
Shugo
S
Ueda
Ichiro
I
Kuwabara
Fu-Tong
FT
Liu
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000098:blood supply / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D005260:Female; D037161:Galectins / Q000235:genetics*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009389:Neovascularization, Pathologic / Q000235:genetics; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
D037161:Galectins; C092525:LGALS7 protein, human; C490487:Lgals7 protein, mouse