Chordin is underexpressed in ovarian tumors and reduces tumor cell motility

FASEB J. 2006 Feb;20(2):240-50. doi: 10.1096/fj.05-4126com.

Abstract

Ovarian cancers mostly derive from the monolayer epithelium that covers the ovary. There are currently very few molecular clues to the etiology of this cancer. Bone morphogenetic proteins (BMPs) are required for follicular development and female fertility and are expressed in the ovarian surface epithelium (OSE). We previously reported the expression of human chordin (CHRD), a BMP extracellular regulator, in the ovary. Here we show that CHRD is underexpressed in epithelium ovary cancer and epithelial cancer cell lines as compared with normal tissues and OSE, respectively. Besides, we detected BMP expression in all ovarian cell lines analyzed. To determine the functional relevance of the absence of CHRD mRNA in tumors and cancer cell lines, we studied the effects of CHRD on two cancer cell lines, BG1 and PEO14. Migratory and invasive properties were greatly reduced, whereas cell adhesion to the support was enhanced. In addition, we detected chordin (Chrd) expression in OSE of rat ovaries in a pattern similar to that of BMP4. Altogether, these results suggest that CHRD could participate in regulating BMP activity in normal OSE physiology, and that its mis-expression in OSE may facilitate cancer incidence and/or progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion
  • Cell Line, Tumor
  • Cell Movement*
  • Epithelial Cells / metabolism
  • Female
  • Gene Dosage
  • Gene Expression Regulation, Neoplastic*
  • Glycoproteins / genetics
  • Glycoproteins / metabolism*
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Neoplasm Invasiveness
  • Ovarian Cysts / genetics
  • Ovarian Cysts / metabolism
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology*
  • Ovary / cytology
  • Ovary / metabolism*
  • Rats

Substances

  • Glycoproteins
  • Intercellular Signaling Peptides and Proteins
  • chordin