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Integrin-mediated action of insulin-like growth factor binding protein-2 in tumor cells

B S Schütt1, M Langkamp, U Rauschnabel

  • 1Pediatric Endocrinology Section, University Children's Hospital, 72076 Tuebingen, Germany.

Journal of Molecular Endocrinology
|June 3, 2004
PubMed

Insights

Insulin-like growth factor binding protein-2 (IGFBP-2) promotes tumor cell de-adhesion and reduces proliferation by interacting with alpha5beta1-integrin, independent of insulin-like growth factors (IGFs). This suggests a novel therapeutic target for aggressive cancers.

Area of Science:

  • Oncology
  • Cell Biology
  • Biochemistry

Background:

  • Neoplastic production of insulin-like growth factor binding protein-2 (IGFBP-2) correlates with tumor malignancy.
  • IGFBP-2 possesses an RGD motif, suggesting potential IGF-independent interactions with cell surface receptors like integrins.

Purpose of the Study:

  • To investigate the hypothesis that IGFBP-2 interacts with tumor cells via integrins, independent of IGF signaling.
  • To examine the effects of IGFBP-2 on integrin binding, intracellular signaling, cell adhesion, and proliferation in tumor cell lines.

Main Methods:

  • Tracer displacement studies using radiolabeled IGFBP-2.
  • Blocking experiments with integrin antibodies and fibronectin.
  • Analysis of focal adhesion kinase (FAK) and MAP-kinase phosphorylation.
  • Assessment of cell adhesion and proliferation rates.

Main Results:

  • Specific binding of IGFBP-2 to tumor cells was observed, mediated by alpha5beta1-integrin.
  • IGFBP-2 binding led to dephosphorylation of FAK and p42/44 MAP-kinases.
  • IGFBP-2 dose-dependently promoted cell de-adhesion and reduced proliferation.
  • These effects occurred independently of IGF-I and IGF-II, even in cells lacking functional IGF-I receptors.

Conclusions:

  • IGFBP-2 can exert biological effects on tumor cells through an IGF-independent mechanism involving alpha5beta1-integrin.
  • This interaction influences crucial cellular processes like adhesion and proliferation, highlighting IGFBP-2 as a potential therapeutic target in aggressive cancers.

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