Abstract
There is a critical need to develop effective new strategies for diagnosis and treatment of ovarian cancer. In the present work, we investigated the expression of galectin-7 (gal-7) in epithelial ovarian cancer (EOC) cells and studied its functional relevance. Immunohistochemical analysis of gal-7 expression in tissue microarrays showed that while gal-7 was not detected in normal ovarian tissues, positive cytoplasmic staining of gal-7 was detected in epithelial cells in all EOC histological subtypes but was more frequent in high grade tumors and metastatic samples. Gal-7 expression correlated with a significant difference in the overall survival of patients with ovarian serous cystadenocarcinoma. Furthermore, using human EOC cell lines, we found that gal-7 expression was induced by mutant p53. Mechanistically, Matrigel invasion assays and live cell imaging showed that gal-7 increased the invasive behavior of ovarian cancer cells by inducing MMP-9 and increasing cell motility. EOC cells can also secrete gal-7. Recombinant human gal-7 kills Jurkat T cells and human peripheral T cells, suggesting that gal-7 also has immunosuppressive properties. Taken together, our study validates the clinical significance of gal-7 overexpression in ovarian cancer and provides a rationale for targeting gal-7 to improve the outcome of patients with this disease.
Highlights
Epithelial ovarian cancer (EOC) accounts for approximately 85–90% of total ovarian cancers and is the leading cause of gynecologic malignancies in North America and worldwide [1]
Our study validates the clinical significance of gal-7 overexpression in ovarian cancer and provides a rationale for targeting gal-7 to improve the outcome of patients with this disease
To study the role of gal-7 in ovarian cancer, we first conducted an in silico analysis of gal-7 gene expression in EOC cells using publically available datasets from the Gene Expression Omnibus (GEO) repository of the National Center for Biotechnology Information (NCBI)
Summary
Epithelial ovarian cancer (EOC) accounts for approximately 85–90% of total ovarian cancers and is the leading cause of gynecologic malignancies in North America and worldwide [1]. Members of the galectin family are recognized for their ability to bind β-galactosides via their carbohydrate recognition domain (CRD) They play an important role in several physiological processes including cell migration, programmed cell death and regulation of the immune response (as reviewed in [2]). They are involved in a number of pathological conditions including cancer. Gal-7 is strictly expressed in epithelial cells This galectin is generally considered to be a marker of epithelial differentiation. It is present in normal epithelial cells of various tissues and is rarely expressed in any other cell types including hematopoietic cells, muscle cells, neurons, www.impactjournals.com/oncotarget
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