Caveolin-1 inhibits breast cancer growth and metastasis.
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.
Sloan
Erica K
EK
Peter MacCallum Cancer Centre, Locked Bag #1, A'Beckett Street, Melbourne, Victoria 8006, Australia.
Stanley
Kym L
KL
Anderson
Robin L
RL
D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D051242:Caveolin 1; D022461:Caveolins / Q000235:genetics / Q000502:physiology*; D002455:Cell Division / Q000235:genetics*; D005260:Female; D006801:Humans; D051379:Mice; D023421:Models, Animal; D009362:Neoplasm Metastasis / Q000473:pathology
C495540:CAV1 protein, human; C495541:Cav1 protein, mouse; D051242:Caveolin 1; D022461:Caveolins