Prostate cancer-derived angiogenin stimulates the invasion of prostate fibroblasts - Abstract

Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.

Prostate fibroblasts promote prostate cancer progression by secreting factors that enhance tumor growth and induce the migration and invasion of prostate cancer cells. Considering the role of fibroblasts in cancer progression, we hypothesized that prostate cancer cells recruit these cells to their vicinity, where they are most directly available to influence cancer cell behavior. To test this hypothesis, we performed modified Boyden chamber assays assessing the migration and collagen I invasion of normal primary prostate fibroblasts (PrSCs) and prostate cancer-associated fibroblasts (PCAFs) in response to media conditioned by the metastatic prostate cancer cell lines PC-3, LNCaP, and DU145. During 4-h incubations, PrSCs and PCAFs migrated and invaded in response to the conditioned media. To identify candidate proteins in the conditioned media that produced these effects, we performed cytokine antibody arrays and detected angiogenin in all three media. Angiogenin-blocked PC-3-conditioned medium, obtained using an anti-angiogenin polyclonal antibody or angiogenin siRNA, significantly reduced PC-3-induced PrSC and PCAF collagen I invasion. Furthermore, angiogenin alone at 1, 2, and 5 ng/mL significantly stimulated PCAF collagen I invasion. These results suggest that PC-3-derived angiogenin stimulates the invasion of normal prostate fibroblasts and prostate cancer-associated fibroblasts and is sufficient for invasion of the latter. Since prostate fibroblasts play key roles in prostate cancer progression, targeting their invasion using an anti-angiogenin-based therapy may be a strategy for preventing or treating advanced prostate cancer.

Written by:
Jones ML, Ewing CM, Isaacs WB, Getzenberg RH.   Are you the author?

Reference: J Cell Mol Med. 2011 Feb 25. Epub ahead of print.
doi: 10.1111/j.1582-4934.2011.01283.x

PubMed Abstract
PMID: 21352472

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