Galectin-1-mediated tumor invasion and metastasis, up-regulated matrix metalloproteinase expression, and reorganized actin cytoskeletons.

Abstract

Galectin-1 (Gal-1) is a beta-galactose-binding lectin; its expression level has been reported to correlate with tumor progression. Gal-1 is highly expressed in the invasive front of primary tumors and in the cancer cells of metastatic lesions in the lymph nodes of patients with oral squamous cell carcinoma. However, the molecular mechanism of Gal-1 in tumor metastasis is not completely clear. We found that increased Gal-1 expression is closely associated with its high levels of invasion in lung adenocarcinoma and oral squamous cell carcinoma cell lines. Knocking down Gal-1 with small interfering RNA in highly invasive cancer cells reduced their invasion levels. Moreover, the invasion ability of poorly invasive cancer cells was significantly increased after Gal-1 overexpression of Gal-1. Mechanism studies revealed that Gal-1 promoted tumor invasion mainly by up-regulating matrix metalloproteinase (MMP)-9 and MMP-2 and by reorganizing actin cytoskeleton. Gal-1 enhanced the activation of Cdc42, a small GTPase and member of the Rho family, thus increasing the number and length of filopodia on tumor cells. Furthermore, Gal-1-overexpressing cells had higher metastatic abilities in tail vein metastasis assays in vivo. We conclude that Gal-1 is involved in tumor invasion and metastasis by increasing MMP expression and reorganizing cytoskeletons in oral cancers and lung adenocarcinoma.

• Authors: Ming-Heng Wu, Tse-Ming Hong, Hui-Wen Cheng, Szu-Hua Pan, Yu-Ray Liang, Hsiao-Chin Hong, Wei-Fan Chiang, Tung-Yiu Wong, Dar-Bin Shieh, Ai-Li Shiau, Ying-Tai Jin, Yuh-Ling Chen
• Journal: Molecular cancer research : MCR (Mol Cancer Res) Vol. 7 Issue 3 Pg. 311-8 (Mar 2009) ISSN: 1541-7786 [Print] United States
• PMID: 19276182 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Actins
• Galectin 1
• RNA, Small Interfering
• Matrix Metalloproteinase 2
• Matrix Metalloproteinase 9
• rho GTP-Binding Proteins

Topics

• Actins (metabolism)
• Adenocarcinoma (genetics, metabolism, pathology)
• Animals
• Carcinoma, Squamous Cell (genetics, metabolism, pathology)
• Cell Line, Tumor
• Cytoskeleton (metabolism)
• Galectin 1 (biosynthesis, genetics)
• Humans
• Lung Neoplasms (genetics, metabolism, pathology)
• Male
• Matrix Metalloproteinase 2 (biosynthesis, genetics, metabolism)
• Matrix Metalloproteinase 9 (biosynthesis, genetics, metabolism)
• Mice
• Mouth Neoplasms (genetics, metabolism, pathology)
• Neoplasm Invasiveness
• Neoplasms (enzymology, genetics, metabolism, pathology)
• RNA, Small Interfering (genetics)
• Up-Regulation
• rho GTP-Binding Proteins (metabolism)