Caveolin-1 reduces osteosarcoma metastases by inhibiting c-Src activity and Met signaling

Lara Cantiani, Maria Cristina Manara, Cinzia Zucchini, Paola De Sanctis, Monia Zuntini, Luisa Valvassori, Massimo Serra, Martina Olivero, Maria Flavia Di Renzo, Mario Paolo Colombo, Piero Picci, Katia Scotlandi

Research output: Contribution to journalArticlepeer-review

Abstract

Caveolin-1 (Cav-1) is highly expressed in normal osteoblasts. This article reports that Cav-1 down-regulation is part of osteoblast transformation and osteosarcoma progression and validates its role as oncosuppressor in human osteosarcoma. A survey of 6-year follow-up indicates a better overall survival for osteosarcoma expressing a level of Cav-1 similar to osteoblasts. However, the majority of primary osteosarcoma shows significantly lower levels of Cav-1 than normal osteoblasts. Accordingly, Met-induced osteoblast transformation is associated with Cav-1 down-regulation. In vitro, osteosarcoma cell lines forced to overexpress Cav-1 show reduced malignancy with inhibited anchorage- independent growth, migration, and invasion. In vivo, Cav-1 overexpression abrogates the metastatic ability of osteosarcoma cells. c-Src and c-Met tyrosine kinases, which are activated in osteosarcoma, colocalize with Cav-1 and are inhibited on Cav-1 overexpression. Thus, Cav-1 behaves as an oncosuppressor in osteosarcoma. Altogether, data suggest that Cav-1 down-modulation might function as a permissive mechanism, which, by unleashing c-Src and Met signaling, enables osteosarcoma cells to invade neighboring tissues. These data strengthen the rationale to target c-Src family kinases and/or Met receptor to improve the extremely poor prognosis of metastatic osteosarcoma.

Original languageEnglish
Pages (from-to)7675-7685
Number of pages11
JournalCancer Research
Volume67
Issue number16
DOIs
Publication statusPublished - Aug 15 2007

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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