SPARC inhibits LPA-mediated mesothelial-ovarian cancer cell crosstalk

Neveen A. Said, Ida Najwer, Matthew J. Socha, David J. Fulton, Samuel C. Mok, Kouros Motamed

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

The interplay between peritoneal mesothelial cells and ovarian cancer cells is critical for the initiation and peritoneal dissemination of, and ascites formation in, ovarian cancer. The production of lysophosphatidic acid (LPA) by both peritoneal mesothelial cells and ovarian cancer cells has been shown to promote metastatic phenotype in ovarian cancer. Herein, we report that exogenous addition or ectopic overexpression of the matricellular protein SPARC (secreted protein acidic and rich in cysteine) significantly attenuated LPA-induced proliferation, chemotaxis, and invasion in both highly metastatic SKOV3 and less metastatic OVCAR3 ovarian cancer cell lines. SPARC appears to modulate these functions, at least in part, through the regulation of LPA receptor levels and the attenuation of extracellular signal-regulated kinase (ERK) 1/2 and protein kinase B/AKT signaling. Moreover, our results show that SPARC not only significantly inhibited both basal and LPA-induced interleukin (IL) 6 production in both cell lines but also attenuated IL-6-induced mitogenic, chemotactic, and proinvasive effects, in part, through significant suppression of ERK1/2 and, to a lesser extent, of signal transducers and activators of transcription 3 signaling pathways. Our results strongly suggest that SPARC exerts a dual inhibitory effect on LPA-induced mesothelial-ovarian cancer cell crosstalk through the regulation of both LPA-induced IL-6 production and function. Taken together, our findings underscore the use of SPARC as a potential therapeutic candidate in peritoneal ovarian carcinomatosis.

Original languageEnglish (US)
Pages (from-to)23-35
Number of pages13
JournalNeoplasia
Volume9
Issue number1
DOIs
StatePublished - Jan 2007

Keywords

  • IL-6
  • LPA
  • Mesothelial cells
  • Ovarian cancer
  • SPARC

ASJC Scopus subject areas

  • Cancer Research

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    Said, N. A., Najwer, I., Socha, M. J., Fulton, D. J., Mok, S. C., & Motamed, K. (2007). SPARC inhibits LPA-mediated mesothelial-ovarian cancer cell crosstalk. Neoplasia, 9(1), 23-35. https://doi.org/10.1593/neo.06658