Overexpression of Galectin-7, A Myoepithelial Cell Marker, Enhances Spontaneous Metastasis of Breast Cancer Cells

Abstract

Galectins are members of a family of ␤-galactosidesbinding proteins that have recently emerged as novel modulators in different aspects of cancer. The expression of galectins in tumors and/or the tissue surrounding them has been well documented. Since galectin-7 expression has been associated with epithelial tissues and varies significantly in various types of cancer, we have investigated for the first time its role in breast cancer. Using two preclinical mouse models, high levels of galectin-7 expression in breast cancer cells drastically increased their ability to metastasize to lungs and bones. Significant increases in the number of pulmonary metastases and osteolytic lesions were induced by overexpression of galectin-7 compared with control cells. In human tissues, galectin-7 was specifically found in myoepithelial cells of normal human breast tissue, but not in luminal cells. Its expression was severely altered in breast carcinoma, many samples showing greater than 70% of galectin-7 positive cells. High expression levels of galectin-7 were restricted to high-grade breast carcinomas, including HER2 overexpressing and basal-like groups. In HER2 overexpressing cases, galectin-7 expression was associated with lymph node axillary metastasis. Taken together, our results indicate that galectin-7 may represent a potential target for both specific detection and therapeutic inhibition of metastatic breast cancer.

Intracellular galectins in cancer cells: Potential new targets for therapy

“…In contrast, it seems to induce apoptosis in other B-cell lymphomas (81). Galectin-7 displays a dual functionality in apoptosis as well since it reduces chemosensitivity in melanomas, breast and lymphoid cancer cells, yet it sensitizes colon, urothelial and cervical cancer cells to cell death (82)(83)(84)(85)(86)(87). This role of galectin-7 in melanoma cells is clearly distinct from that of galecin-9 which rather promotes death of melanoma cells (35,88).…”

“…Further, conflicting functionalities are once again displayed in the case of galectin-7 dependent on the cell type. Particularly, galectin-7 reduces migration of gastric cancer cells and invasion of urothelial and gastric cancer cells (85,103) while it is associated with increased invasion of other types of cancer, including breast cancer and T-cell lymphoma (82,(127)(128)(129)(130). Galectin-8 also seems to have different abilities to modulate migration, most notably in glioblastoma and colon cancer Decrease expression of TGF-β responsive genes (195) resulting in an anti-fibrotic effect on liver tissue cells (106,131).…”

Roles of Galectin-7 in Cancer

“…This finding suggested galectin-7 as one of the mammary carcinoma specific molecular marker (Lu et al, 1997). A later study using preclinical mouse models also indicated high expression of galectin-7 in breast cancer cells (Demers et al, 2010). This over-expression of galectin-7 was found to increase the metastatic behavior of these cells, rendered them resistant to apoptosis.…”

Galectin-7 promotes the invasiveness of human oral squamous cell carcinoma cells via activation of ERK and JNK signaling

“…Galectin-7 exhibits the ability to modulate the metastatic phenotype of several types of cancer cells (10,12,21). Demers et al (21) demonstrated that ectopic expression of galectin-7 increases the invasiveness of lymphoma, accelerates the development of thymic lymphoma, and previously identified that overexpressing galectin-7 enhances the metastatic growth of breast cancer cells in the lungs and bones in two different mouse models (10). Enforced expression of galectin-7 also promotes the invasiveness of human HeLa cervical epithelial adenocarcinoma cells (12).…”

“…For example, in human gastric cancer specimens, galectin-7 is underexpressed due to epigenetic modifications and this suppresses the proliferation and invasion of gastric cancer cells (9). By contrast, in high-grade breast cancer galectin-7 is overexpressed, facilitating the spontaneous metastasis of breast cancer cells in preclinical mouse models (10). The tumor-promoting role of galectin-7 has also been noted in ovarian cancer cells (11) and cervical cancer cells (12).…”