Caveolin-1 secreting LNCaP cells induce tumor growth of caveolin-1 negative LNCaP cells in vivo.

Caveolin-1 (Cav-1) was originally identified as a structural protein of caveolae, which is a plasma membrane domain that regulates a variety of signaling pathways involved in cell growth and migration. Here, we show that expression of Cav-1 in the Cav-1-deficient human prostate cancer cell line LNCaP both stimulates cell proliferation and promotes tumor growth in nude mice. Unexpectedly, Cav-1 expressing LNCaP (LNCaP(Cav-1)) cells injected into one side of a nude mouse promoted tumor growth of Cav-1 negative LNCaP cells injected on the contralateral side of the same animal. The LNCaP tumors were positive for Cav-1, however, this signal was not caused by migrated LNCaP(Cav-1) cells, but we show that this Cav-1 was secreted by the LNCaP(Cav-1) tumors. We demonstrate that conditioned media from LNCaP(Cav-1) cells contained Cav-1 that was associated with a lipoprotein particle ranging in size from 15 to 30 nm and a density similar to high density lipoprotein particle. These results suggest that LNCaP(Cav-1) cells secreting Cav-1 particle produce an endocrine factor that stimulates tumor growth. (c) 2007 Wiley-Liss, Inc.