The lymphotactin receptor is expressed in epithelial ovarian carcinoma and contributes to cell migration and proliferation

Mol Cancer Res. 2012 Nov;10(11):1419-29. doi: 10.1158/1541-7786.MCR-12-0361. Epub 2012 Sep 10.

Abstract

Chemokine receptor-ligand interactions are important to support functioning of both normal and pathologic cells. The expression and function of chemokine receptors in epithelial ovarian carcinoma (EOC) is largely unknown. Here, we report that the lymphotactin receptor (XCR1) was expressed in primary and metastatic human epithelial ovarian carcinoma (EOC) specimens and cell lines. In contrast, expression of XCR1 was not detected in the normal ovary or in human normal ovarian surface epithelial cells. Our data indicate that XCL1 and XCL2 are either present in the malignant ascites or expressed by the ovarian carcinoma cells. The addition of lymphotactin (XCL1 and XCL2) stimulated migration and proliferation of XCR1-positive cells. Reduction of XCR1 expression in ovarian carcinoma cell line SKOV-3 resulted in abrogated diaphragm and peritoneal wall tumor formation and in reduced frequency of colonic, splenetic, and liver nodules in an in vivo xenograft mouse model. Taken together, our data suggest that XCR1 is expressed early during the course of tumorigenic transformation and contributes towards increased cell migration and proliferation, which can facilitate the prometastatic behavior of EOC cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Ovarian Epithelial
  • Cell Growth Processes / physiology
  • Cell Line, Tumor
  • Cell Movement / physiology*
  • Chemokines, C / biosynthesis
  • Chemokines, C / genetics
  • Female
  • Humans
  • Lymphokines / metabolism
  • Mice
  • Mice, Nude
  • Neoplasms, Glandular and Epithelial / genetics
  • Neoplasms, Glandular and Epithelial / metabolism*
  • Neoplasms, Glandular and Epithelial / pathology*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology*
  • Receptors, G-Protein-Coupled / biosynthesis*
  • Receptors, G-Protein-Coupled / genetics
  • Sialoglycoproteins / metabolism
  • Tissue Array Analysis
  • Transplantation, Heterologous

Substances

  • Chemokines, C
  • Lymphokines
  • Receptors, G-Protein-Coupled
  • Sialoglycoproteins
  • XCL1 protein, human
  • XCL2 protein, human
  • XCR1 protein, human
  • lymphotactin