¹Peter MacCallum Cancer Centre, Locked Bag #1, A'Beckett Street, Melbourne, Victoria 8006, Australia

Correspondence: RL Anderson, E-mail: robin.anderson@petermac.org

²Current address: Division of Hematology-Oncology, UCLA School of Medicine, Los Angeles CA 90095-1678, USA

Received 24 March 2004; Revised 16 June 2004; Accepted 16 July 2004; Published online 30 August 2004.

Abstract

Caveolin-1 was identified in a screen for genes involved in breast cancer progression. Caveolin-1 is the major protein component of caveolae, flask-shaped invaginations found in a number of different cell types. Using an orthotopic model of spontaneous breast cancer metastasis, caveolin-1 was found to be expressed in low and non-metastatic primary tumors, but at much lower levels in highly metastatic 4T1.2 and 4T1.13 tumors. Exogenous expression of caveolin-1 at moderate levels in 4T1.2 cells was sufficient to suppress primary tumor growth after inoculation of cells into the mammary gland. Expression of high levels of caveolin-1 also inhibited subsequent metastasis to distant organs. Cells expressing high levels of caveolin-1 showed reduced capacity to invade Matrigel, diminished response to laminin-1 stimulation and decreased metastasis to lung and bone. This study provides the first functional evidence that caveolin-1 regulates primary breast tumor growth and spontaneous metastasis of breast cancer.