Urokinase receptor interacts with α(v)β5 vitronectin receptor, promoting urokinase-dependent cell migration in breast cancer

Maria V. Carriero, Silvana Del Vecchio, Monica Capozzoli, Paola Franco, Laura Fontana, Antonella Zannetti, Gerardo Botti, Giuseppe D'Aiuto, Marco Salvatore, M. Patrizia Stoppelli

Research output: Contribution to journalArticlepeer-review

Abstract

Perturbation of adhesive interactions at cell-substratum and cell-cell contact sites is a critical event in the multistep process of cancer invasion. Recent studies indicate that the urokinase receptor (uPAR) is associated in large molecular complexes with other molecules, such as integrins. To test the possibility that uPAR may physically and functionally interact with vitronectin (V(n)) receptors, we determined the expression level of uPAR, αvβ3, and αvβ5 V(n) receptors in 10 human breast carcinomas. Here, we show the ability of uPAR to physically associate with α(v)β5 in the breast carcinomas examined. The functional effects of this interaction were studied using HT1080 human fibrosarcoma and MCF-7 human breast carcinoma cell lines, both exhibiting a urokinase-dependent physical association between uPAR and α(v)β5. Both cell lines respond to urokinase or to its noncatalytic amino-terminal fragment by exhibiting remarkable cytoskeletal rearrangements that are mediated by α(v)β5 and require protein kinase C activity. On the contrary, binding of Vn to α(v)β5 results in the protein kinase C-independent formation of F-actin containing microspike-type structures. Furthermore, α(v)β5 is required for urokinase- directed, receptor-dependent MCF-7 and HT1080 cell migration. These data show that uPAR association with α(v)β5 leads to a functional interaction of these receptors and suggest that uPAR directs cytoskeletal rearrangements and cell migration by altering α(v)β5 signaling specificity.

Original languageEnglish
Pages (from-to)5307-5314
Number of pages8
JournalCancer Research
Volume59
Issue number20
Publication statusPublished - Oct 15 1999

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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