Suppression of Tumor Growth by Galectin-7 Gene Transfer

Abstract

Galectin-7 is a ␤-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.

A Novel Function for Galectin-7: Promoting Tumorigenesis by Up-regulatingMMP-9Gene Expression

“…Together with our previous results showing that galectin-7 was associated with lymphoma aggressiveness (9), the results of our study were unanticipated in that galectin-7 has been thus far mostly considered as a marker for epithelial stratification during development and associated with proapoptotic functions in keratinocytes (12)(13)(14). Moreover, recent studies have shown that overexpression of galectin-7 in human DLD-1 colon carcinoma cells inhibits their growth when injected s.c. in the immunodeficient SCID mouse model (25). The effect was attributed to the suppression of cell growth and possibly to reduced angiogenesis.…”

Sensitizing Effect of Galectin-7 in Urothelial Cancer to Cisplatin through the Accumulation of Intracellular Reactive Oxygen Species

“…The expression of galectin-7 was identified in normal stratified epithelial cells, including the skin, tongue, esophagus, and Hassal's corpuscles in the thymus, and interestingly, it was strikingly down-regulated in squamous cell carcinoma cells (19). Functionally, the ectopical expression of galectin-7 in colon carcinoma cells rendered the cells more sensitive to several apoptotic stimuli through the activation of JNK (20,21). These findings suggested that galectin-7 played important roles in carcinogenesis or chemosensitivity in squamous cell and colorectal carcinomas, but there were no reports about its expression in urothelial carcinomas.…”

Galectin-7 promotes the invasiveness of human oral squamous cell carcinoma cells via activation of ERK and JNK signaling

“…Previous studies have demonstrated that overexpressing galectin-7 inhibits the proliferation of several specific cancer cells such as gastric cancer cells (9) and colon carcinoma cells (19). However, in other cancer cells including epithelial ovarian cancer (20), galectin-7 was involved in cell proliferation, as its downregulation inhibited the proliferation of A2780-PAR ovarian cancer cell.…”