Bone Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Bone Cancer, including details on symptoms, types, treatment.

Bone-metastatic potential of human prostate cancer cells correlates with Akt/PKB activation by alpha platelet-derived growth factor receptor.

Dolloff NG, Shulby SS, Nelson AV, Stearns ME, Johannes GJ, Thomas JD, Meucci O, Fatatis A

Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, PA 19102, USA.

Prostate adenocarcinoma metastasizes to the skeleton more frequently than any other organ. An underlying cause of this phenomenon may be the ability of bone-produced factors to specifically select disseminated prostate cancer cells that are susceptible to their trophic effects. Platelet-derived growth factor (PDGF), a potent mitogen for both normal and tumor cells, is produced in several tissues including bone, where it is synthesized by both osteoblasts and osteoclasts. Here, we show that PDGF causes a significantly stronger activation of the Akt/PKB survival pathway in bone-metastatic prostate cancer cells compared to nonmetastatic cells. Normal prostate epithelial cells and DU-145 prostate cells, originally derived from a brain metastasis, are not responsive to PDGF. In contrast, epidermal growth factor stimulates Akt to the same extent in all prostate cells tested. This difference in PDGF responsiveness depends on the higher expression of alpha-PDGFR in bone-metastatic compared to nonmetastatic prostate cells and the lack of alpha-PDGFR expression in normal and metastatic prostate cells derived from tissues other than bone. Thus, alpha-PDGFR expression might identify prostate cancer cells with the highest propensity to metastasize to the skeleton.

Published 13 October 2005 in Oncogene, 24(45): 6848-54.
Full-text of this article is available online (may require subscription).

© 2004-2008 Bone Cancer Research Today. All Rights Reserved.