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Induction of antiproliferative connective tissue growth factor expression in Wilms' tumor cells by

Mei-Hong Li1, Teresa Sanchez, Anna Pappalardo

  • 1Center for Vascular Biology, University of Connecticut Health Center, Farmington, Connecticut, USA.

Molecular Cancer Research : MCR
|October 17, 2008
PubMed

Insights

Connective tissue growth factor (CTGF) is regulated by sphingosine-1-phosphate (S1P) via S1P2 in Wilms' tumor cells. Lower CTGF levels in tumors suggest it may act as a Wilms' tumor growth inhibitor.

Area of Science:

  • Biochemistry
  • Oncology
  • Cell Biology

Background:

  • Connective tissue growth factor (CTGF) is a CCN family protein involved in various cellular processes including tumor growth.
  • The specific role and regulation of CTGF in Wilms' tumor pathogenesis are not well understood.

Purpose of the Study:

  • To investigate the role of sphingosine-1-phosphate (S1P) in regulating CTGF expression in Wilms' tumor.
  • To elucidate the signaling pathways involved in S1P-mediated CTGF regulation.
  • To determine the effect of CTGF on Wilms' tumor cell proliferation.

Main Methods:

  • Wilms' tumor cell line (WiT49) treated with S1P and receptor antagonists/agonists.
  • Quantitative real-time PCR and Western blot analysis of CTGF expression.
  • Inhibition studies using ROCK and JNK pathway inhibitors.
  • Cell proliferation assays with recombinant CTGF and CTGF overexpression.

Main Results:

  • Sphingosine-1-phosphate (S1P) induced CTGF expression in WiT49 cells in a concentration- and time-dependent manner, mediated by the S1P2 receptor.
  • S1P-induced CTGF expression involved RhoA/ROCK and c-Jun NH2-terminal kinase (JNK) pathways.
  • CTGF expression was significantly decreased in most Wilms' tumor tissues compared to normal tissues.
  • Recombinant CTGF and CTGF overexpression inhibited WiT49 cell proliferation.

Conclusions:

  • S1P, via S1P2, upregulates CTGF in Wilms' tumor cells, involving RhoA/ROCK and JNK signaling.
  • CTGF may function as a tumor suppressor, inhibiting Wilms' tumor cell growth.
  • These findings suggest a novel regulatory mechanism for CTGF in Wilms' tumor and its potential therapeutic implications.

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