Galectin-3 protects human breast carcinoma cells against nitric oxide-induced apoptosis: implication of galectin-3 function during metastasis

Am J Pathol. 2001 Sep;159(3):1055-60. doi: 10.1016/S0002-9440(10)61780-4.

Abstract

Galectin-3 is a beta-galactoside-binding protein which regulates many biological processes including cell adhesion, migration, cell growth, tumor progression, metastasis, and apoptosis. Although the exact function of galectin-3 in cancer development is unclear, galectin-3 expression is associated with neoplastic progression and metastatic potential. Since studies have suggested that tumor cell survival in microcirculation determines the metastatic outcome, we examined the effect of galectin-3 overexpression in human breast carcinoma cell survival using the liver ischemia/reperfusion metastasis model. While the majority of control cells died by hepatic ischemia/reoxygenation, nearly all of galectin-3 overexpressing cells survived. We showed that galectin-3 inhibits nitrogen free radical-mediated apoptosis, one of the major death pathways induced during hepatic ischemia/reperfusion. Galectin-3 inhibition of apoptosis involved protection of mitochondrial integrity, inhibition of cytochrome c release and caspase activation. Taking these results together with the previous observation that galectin-3 inhibits apoptosis induced by loss of cell adhesion, we propose that galectin-3 is a critical determinant for anchorage-independent and free radical-resistant cell survival during metastasis.

Publication types

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

MeSH terms

  • Animals
  • Antigens, Differentiation / pharmacology*
  • Antigens, Differentiation / physiology
  • Apoptosis / drug effects*
  • Apoptosis / physiology*
  • Breast Neoplasms / complications
  • Breast Neoplasms / pathology
  • Breast Neoplasms / physiopathology*
  • Carcinoma / complications
  • Carcinoma / pathology
  • Carcinoma / physiopathology*
  • Carcinoma / secondary
  • Cell Survival / drug effects
  • Female
  • Galectin 3
  • Humans
  • Ischemia / mortality
  • Ischemia / physiopathology
  • Liver Circulation
  • Mice
  • Mice, Nude
  • Nitric Oxide / physiology*
  • Reperfusion Injury / physiopathology
  • Tumor Cells, Cultured

Substances

  • Antigens, Differentiation
  • Galectin 3
  • Nitric Oxide