Issue 2, 2012

Hedgehog signaling in myofibroblasts directly promotes prostate tumor cell growth

Abstract

Despite strong evidence for the involvement of the stroma in Hedgehog signaling, little is known about the identity of the stromal cells and the signaling mechanisms that mediate the growth promoting effect of Hh signaling. We developed an in vitro co-culture model using microchannel technology to examine the effect of paracrine Hh signaling on proliferation of prostate cancer cells. We show here that activation of Hh signaling in myofibroblasts is sufficient to accelerate tumor cell growth. This effect was independent of any direct effect of Hh ligand on tumor cells or other cellular components of the tumor stroma. Further, the trophic effect of Hh pathway activation in myofibroblasts does not require collaboration of other elements of the stroma or direct physical interaction with the cancer cells. By isolating the tropic effect of Hh pathway activation in prostate stroma, we have taken the first step toward identifying cell-specific mechanisms that mediate the effect of paracrine Hh signaling on tumor growth.

Graphical abstract: Hedgehog signaling in myofibroblasts directly promotes prostate tumor cell growth

Supplementary files

Article information

Article type
Paper
Submitted
12 Sep 2011
Accepted
15 Nov 2011
First published
11 Jan 2012

Integr. Biol., 2012,4, 142-152

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