Galectin-1-Mediated Tumor Invasion and Metastasis, Up-Regulated Matrix Metalloproteinase Expression, and Reorganized Actin Cytoskeletons

Abstract

Galectin-1 (Gal-1) is a B-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. (Mol Cancer Res 2009;7(3):311 -8)

Differential proteomic and phenotypic behaviour of papillary and anaplastic thyroid cell lines

“…Indeed, other proteins in the 8505C cell proteomics are described as associated with the tumour growth and metastatic progression: i.e. the S100A6 [42] and LEG1, which, among several functions, is also considered a co-promoter of MMP-2 and MMP-9 expression [43] and therefore an enhancer of tumour invasion and metastasis. In support of this hypothesis is the observation that the 8505C cells produce and release into the medium a significant quantity of matrix metalloproteinases MMP-2 and MMP-9.…”

Galectin-1 and Its Involvement in Hepatocellular Carcinoma Aggressiveness

“…The role of Gal-1 in molecular mechanisms leading to cancer development has been analyzed in several tumors (11) but surprisingly never in the molecular pathogenesis of HCC. In particular, it is still unknown whether Gal-1 affects the invasive ability of HCC as previously shown in other malignant tumors (25)(26)(27).…”

“…Gal-1 is a multifunctional protein involved in various aspects of tumorigenesis (cell-extracellular matrix and cell-cell interactions, cell migration, angiogenesis, tumor-immune escape) and has been described as a promising cancer target (11)(12)(13). Gal-1 expression has been examined in several malignant tumors (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24), and its correlation with tumor invasiveness and lymph node metastasis was demonstrated in breast cancer (25), neuroblastoma (26), oral squamous cell carcinoma and lung adenocarcinoma (27). Although Kondoh et al (28) showed that the activation of LGALS1 gene expression in HCC results from promoter hypomethylation, data on Gal-1 protein expression in HCC and its correlation to clinicopathological parameters were not available.…”

Lung Cancer-Derived Galectin-1 Mediates Dendritic Cell Anergy through Inhibitor of DNA Binding 3/IL-10 Signaling Pathway

“…Galectin-1, the first discovered protein in the family, has been found to be upregulated in many cancers, including astrocytoma, melanoma, oral, colon, bladder, and ovarian carcinomas (10)(11)(12). Overexpression of galectin-1 in tumors has also been shown to correlate with the aggressiveness of these tumors and the development of metastasis (11)(12)(13). Moreover, recent studies have also suggested that tumors secrete galectin-1, which contributes to the immunosuppressive response and apoptosis of immune cells, particularly T cells (14)(15)(16).…”