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Chemokine receptors in epithelial ovarian cancer.

ABSTRACT: Ovarian carcinoma is the deadliest gynecologic malignancy with very poor rate of survival, and it is characterized by the presence of vast incurable peritoneal metastasis. Studies of the role of chemokine receptors, a family of proteins belonging to the group of G protein-coupled receptors, in ovarian carcinoma strongly placed this family of membrane receptors as major regulators of progression of this malignancy. In this review, we will discuss the roles that chemokine-receptor interactions play to support angiogenesis, cell proliferation, migration, adhesion, invasion, metastasis, and immune evasion in progression of ovarian carcinoma. Data regarding the role that the chemokine receptors play in the disease progression accumulated insofar strongly suggest that this family of proteins could be good therapeutic targets against ovarian carcinoma.

SUBMITTER: Muralidhar GG

PROVIDER: S-EPMC3907814 | biostudies-other | 2013 Dec

REPOSITORIES: biostudies-other

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Chemokine receptors in epithelial ovarian cancer.

Muralidhar Goda G GG Barbolina Maria V MV

International journal of molecular sciences 20131231 1

Ovarian carcinoma is the deadliest gynecologic malignancy with very poor rate of survival, and it is characterized by the presence of vast incurable peritoneal metastasis. Studies of the role of chemokine receptors, a family of proteins belonging to the group of G protein-coupled receptors, in ovarian carcinoma strongly placed this family of membrane receptors as major regulators of progression of this malignancy. In this review, we will discuss the roles that chemokine-receptor interactions pla ...[more]

PMID: 24384839

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Project description:BackgroundLittle is known about the molecules that contribute to the growth of epithelial ovarian carcinomas (EOC), which remain the most lethal gynecological cancer in women. The chemokine Fractalkine/CX(3)CL1 has been widely reported to play a biologically relevant role in tumor growth and spread. We report here the first investigation of the expression and role of CX(3)CL1 in EOC.ResultsEpithelial cells from the surface of the ovary and the Fallopian tubes and from benign, borderline and malignant tumors all stained positive for CX(3)CL1. In tumor specimens from 54 women who underwent surgical treatment for EOC diagnosis, CX(3)CL1 immunoreactivity was unevenly distributed in epithelial tumor cells, and ranged from strong (33%) to absent (17%). This uneven distribution of CX(3)CL1 did not reflect the morphological heterogeneity of EOC. It was positively correlated with the proliferation index Ki-67 and with GILZ (glucocorticoid-induced leucine zipper), previously identified as an activator of the proliferation of malignant EOC cells. Hierarchical clustering analysis, including age at diagnosis, tumor grade, FIGO stage, Ki-67 index, CX(3)CL1, SDF-1/CXCL12 and GILZ immunostaining scores, distinguished two major clusters corresponding to low and high levels of proliferation and differing in terms of GILZ and CX(3)CL1 expression. GILZ overexpression in the carcinoma-derived BG1 cell line resulted in parallel changes in CX(3)CL1 products. Conversely, CX(3)CL1 promoted through its binding to CX(3)CR1 AKT activation and proliferation in BG1 cells. In a mouse subcutaneous xenograft model, the overexpression of GILZ was associated with higher expression of CX(3)CL1 and faster tumor growth.ConclusionOur findings highlight the previously unappreciated constitutive expression of CX(3)CL1 preceding tumorigenesis in ovarian epithelial cells. Together with GILZ, this chemokine emerges as a regulator of cell proliferation, which may be of potential clinical relevance for the selection of the most appropriate treatment for EOC patients.

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Chemokine receptors in epithelial ovarian cancer.

Publications

Chemokine receptors in epithelial ovarian cancer.

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