Akt is Preferentially Expressed in PC‐3 Cells Adhering to Bone Matrix

Abstract

Prostate cancer (PC) commonly metastasizes to the skeleton, where it becomes highly resistant to chemo-therapeutics. The components of the bone extracellular matrix microenvironment and other secreted factors have been implicated in PC cell proliferation. The purpose of this project was to determine the effects of PC-3 cells adhering to bone substrates on Akt activation. PC-3 cells were plated on substrates composed of secreted factors from osteoblastic-like cells (SaOS2), bone stromal-like cells (HS-5), as well as collagen type-1, a major component of the bone matrix, and fibronectin. Western analysis was performed to resolve the phosphorylated Akt. We hypothesize that prostate cancer cells grown on the substrate of secreted factors from osteoblastic (SaOS2) and bone stromal (HS-5) cells will preferentially stimulate the activation of Akt. Also we hypothesize that PC-3 cells grown on type-1 collagen will preferentially stimulate Akt activation rather than grown on fibronectin. Western blot analysis of Akt activation showed the greatest increase in PC-3 cells on SaOS-2 secreted substrate compared to the control (plastic) and HS-5 conditioned media. In addition, we present data showing that Akt is activated preferentially on collagen-type 1 compared to fibronectin. Lastly, we demonstrate that ErbB2 is preferentially expressed on PC-3 cells grown on soluble bone-marrow extracts compared to kidney extracts. These data suggest that secreted factors, including collagen type I, predominately from osteoblastic cells, enhance prostate cancer cell survival in the bone microenvironment and these factors may contribute to drug resistance.