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.
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Acknowledgements
We thank Dr M Tavaria for establishing the RTQ–PCR assay for tumor burden, Ms A Herr for assistance with microscopy, the Peter Mac Microarray Facility for assistance with the cDNA arrays, Dr N Pouliot, Ms C Restall and Dr R Parton for constructive discussions. The kind donation of cells and reagents from Dr Fred Miller, Dr Gary Nolan and Dr Richard Anderson is acknowledged. This work was supported by a Susan Komen Foundation Dissertation Award (EKS) and by grants from the US Department of Army (DAMD17-98-1-8144) (RLA) and the NCI/NIH (ROI CA 90291) (RLA).
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Sloan, E., Stanley, K. & Anderson, R. Caveolin-1 inhibits breast cancer growth and metastasis. Oncogene 23, 7893–7897 (2004). https://doi.org/10.1038/sj.onc.1208062
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DOI: https://doi.org/10.1038/sj.onc.1208062
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