Growth factor-dependent activation of αvβ3 integrin in normal epithelial cells: Implications for tumor invasion

Livio Trusolino, Guido Serini, Germana Cecchini, Cristina Besati, Francesco Saverio Ambesi-Impiombato, Pier Carlo Marchisio, Rosaria De Filippi

Research output: Contribution to journalArticle

Abstract

Integrin activation is a multifaceted phenomenon leading to increased affinity and avidity for matrix ligands. To investigate whether cytokines produced during stromal infiltration of carcinoma cells activate nonfunctional epithelial integrins, a cellular system of human thyroid clones derived from normal glands (HTU-5) and papillary carcinomas (HTU-34) was employed. In HTU-5 cells, αvβ3 integrin was diffused all over the membrane, disconnected from the cytoskeleton, and unable to mediate adhesion. Conversely, in HTU-34 cells, αvβ3 was clustered at focal contacts (FCs) and mediated firm attachment and spreading. αvβ3 recruitment at FCs and ligand- binding activity, essentially identical to those of HTU-34, occurred in HTU- 5 cells upon treatment with hepatocyte growth factor/scatter factor (HGF/SF). The HTU-34 clone secreted HGF/SF and its receptor was constitutively tyrosine phosphorylated suggesting an autocrine loop responsible for αvβ3 activated state. Antibody-mediated inhibition of HGF/SF function in HTU-34 cells disrupted αvβ3 enrichment at FCs and impaired adhesion. Accordingly, activation of αvβ3 in normal cells was produced by HTU-34 conditioned medium on the basis of its content of HGF/SF. These results provide the first example of a growth factor-driven integrin activation mechanism in normal epithelial cells and uncover the importance of cytokine-based autocrine loops for the physiological control of integrin activation.

Original languageEnglish
Pages (from-to)1145-1156
Number of pages12
JournalJournal of Cell Biology
Volume142
Issue number4
DOIs
Publication statusPublished - Aug 24 1998

Keywords

  • c-Met
  • Hepatocyte growth factor/scatter factor
  • Integrins
  • Thyroid
  • Tumor invasion

ASJC Scopus subject areas

  • Cell Biology

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