Galectin-3 protects human breast carcinoma cells against nitric oxide-induced apoptosis: implication of galectin-3 function during metastasis.
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.
Moon
B K
BK
Department of Anesthesiology, Ajou University School of Medicine, Suwon, Korea.
Lee
Y J
YJ
Battle
P
P
Jessup
J M
JM
Raz
A
A
Kim
H R
HR
D000818:Animals; D000943:Antigens, Differentiation / Q000494:pharmacology* / Q000502:physiology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology*; D001943:Breast Neoplasms / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D002277:Carcinoma / Q000150:complications / Q000473:pathology / Q000503:physiopathology* / Q000556:secondary; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D037502:Galectin 3; D006801:Humans; D007511:Ischemia / Q000401:mortality / Q000503:physiopathology; D008102:Liver Circulation; D051379:Mice; D008819:Mice, Nude; D009569:Nitric Oxide / Q000502:physiology*; D015427:Reperfusion Injury / Q000503:physiopathology; D014407:Tumor Cells, Cultured
D000943:Antigens, Differentiation; D037502:Galectin 3; D009569:Nitric Oxide