Combined lysophosphatidic acid/platelet-derived growth factor signaling triggers glioma cell migration in a

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Katrin Lange1, Martial Kammerer, Falk Saupe

  • 1Institute of Biochemistry and Genetics, Department of Biomedicine, University of Basel, Basel, Switzerland.

Cancer Research
|September 2, 2008
PubMed

Insights

Lysophosphatidic acid (LPA) and platelet-derived growth factor (PDGF) promote glioma cell spreading and migration via a novel pathway. This tenascin-C (TN) and fibronectin (FN) interaction offers potential cancer diagnostic and therapeutic targets.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Tenascin-C (TN) inhibits cell spreading by blocking syndecan-4, preventing focal adhesion kinase (FAK) activation and promoting protein degradation.
  • Understanding alternative pathways for cell migration is crucial for cancer research.

Purpose of the Study:

  • To investigate the mechanisms by which lysophosphatidic acid (LPA) and platelet-derived growth factor (PDGF) induce glioma cell spreading and migration.
  • To identify key molecular players and signaling pathways involved in this process on a fibronectin/tenascin-C (FN/TN) substratum.

Main Methods:

  • Gene silencing techniques were employed to assess the necessity of specific proteins (paxillin, tropomyosin 1, 2, and 3).
  • Analysis of signaling pathway involvement, including phosphatidylinositol 3-kinase, RhoKinase, and MAPK/ERK kinase 1/2.
  • RNA microarray analysis to identify expression patterns of TN, PDGF, LPA, and their receptors in various cancers.

Main Results:

  • Simultaneous LPA and PDGF signaling triggers glioma cell spreading and migration independently of syndecan-4.
  • This process involves the activation of paxillin and FAK, and stabilization of RhoA, TM1, TM2, and TM3.
  • Paxillin, TM1, TM2, and TM3 were found to be essential for LPA/PDGF-induced cell spreading on FN/TN.
  • The pathway is dependent on PI3K, RhoKinase, and MAPK/ERK kinase 1/2, but not PLC or JNK.

Conclusions:

  • A novel TN/LPA/PDGF signaling axis promotes glioma cell migration, distinct from the previously known TN/syndecan-4 pathway.
  • This axis is active in malignant tumors, suggesting potential diagnostic and therapeutic applications.
  • Targeting this pathway could offer new strategies for cancer treatment.

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