S1P stimulates chemotactic migration and invasion in OVCAR3 ovarian cancer cells

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Assessment of Ovarian Cancer Spheroid Attachment and Invasion of Mesothelial Cells in Real Time

Published on: May 20, 2014

Kyoung Sun Park1, Mi-Kyoung Kim, Ha Young Lee

  • 1Department of Biochemistry, College of Medicine, Dong-A University, Busan 602-714, Republic of Korea.

Biochemical and Biophysical Research Communications
|March 14, 2007
PubMed

Insights

Sphingosine 1-phosphate (S1P) stimulates ovarian cancer cell migration and invasion through specific S1P receptors. These processes involve G-protein signaling pathways and are inhibited by VPC 23019, suggesting potential therapeutic targets.

Area of Science:

  • Cell Biology
  • Molecular Pharmacology
  • Cancer Research

Background:

  • Ovarian cancer cells (OVCAR3) express sphingosine 1-phosphate (S1P) receptors S1P(1), S1P(2), and S1P(3).
  • S1P signaling pathways are implicated in various cellular processes, including cancer cell behavior.

Purpose of the Study:

  • To investigate the role of S1P receptors in OVCAR3 cell migration and invasion.
  • To elucidate the signaling mechanisms underlying S1P-induced cellular responses in ovarian cancer.

Main Methods:

  • Stimulation of OVCAR3 cells with S1P and measurement of intracellular calcium.
  • Assessment of S1P-mediated activation of extracellular signal-regulated kinase, p38 kinase, and Akt.
  • Analysis of S1P-induced chemotactic migration and invasion using inhibitors like VPC 23019, LY294002, and SB203580.
  • Pertussis toxin (PTX) treatment to assess the role of G(i) proteins.

Main Results:

  • S1P induced intracellular calcium increases, partially inhibited by VPC 23019 (S1P(1/3) antagonist).
  • S1P-induced calcium increases and kinase activations (ERK, p38, Akt) were mediated by phospholipase C and PTX-sensitive G-proteins.
  • S1P stimulated OVCAR3 cell chemotactic migration and invasion in a PTX-sensitive manner.
  • VPC 23019, LY294002, and SB203580 significantly inhibited S1P-induced migration and invasion.

Conclusions:

  • S1P promotes OVCAR3 cell chemotactic migration and invasion.
  • G(i) protein signaling pathways are crucial for S1P-mediated cellular responses.
  • VPC 23019-sensitive S1P receptor(s) are involved in S1P-induced migration and invasion, suggesting their potential as therapeutic targets in ovarian cancer.

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