Suppression of tumor growth by galectin-7 gene transfer

Cancer Res. 2004 Aug 15;64(16):5672-6. doi: 10.1158/0008-5472.CAN-04-0985.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Cell Division / genetics
  • Cell Line, Tumor
  • Colonic Neoplasms / blood supply
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / pathology*
  • Colonic Neoplasms / therapy
  • Female
  • Galectins / genetics*
  • Gene Transfer Techniques
  • Genetic Therapy / methods
  • Humans
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Neovascularization, Pathologic / genetics
  • Transfection
  • Xenograft Model Antitumor Assays

Substances

  • Galectins
  • LGALS7 protein, human
  • Lgals7 protein, mouse