Bone Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Bone Cancer, including details on symptoms, types, treatment.

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

Cantiani L, Manara MC, Zucchini C, De Sanctis P, Zuntini M, Valvassori L, Serra M, Olivero M, Di Renzo MF, Colombo MP, Picci P, Scotlandi K

Laboratory of Oncology Research, Rizzoli Orthopaedic Institute, Italy.

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.

Published 16 August 2007 in Cancer Res, 67(16): 7675-85.
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