Hedgehog signaling in myofibroblasts directly promotes prostate tumor cell growth.
Submitted by Maribella Domenech on
Title | Hedgehog signaling in myofibroblasts directly promotes prostate tumor cell growth. |
Publication Type | Journal Article |
Year of Publication | 2012 |
Authors | Domenech, M, Bushman, W, Beebe, DJ |
Secondary Authors | Bjerregaard, R |
Journal | Integr Biol (Camb) |
Volume | 4 |
Issue | 2 |
Pagination | 142-52 |
Date Published | 2012 Feb |
ISSN | 1757-9708 |
Keywords | Cell Differentiation, Cell Growth Processes, Cell Line, Tumor, Coculture Techniques, Hedgehog Proteins, Humans, Immunohistochemistry, Male, Microscopy, Fluorescence, Myofibroblasts, Paracrine Communication, Prostatic Neoplasms, Real-Time Polymerase Chain Reaction, Receptors, Cell Surface, RNA, Signal Transduction, Stromal Cells, Transcription Factors |
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. |
DOI | 10.1039/c1ib00104c |
Alternate Journal | Integr Biol (Camb) |
PubMed ID | 22234342 |
PubMed Central ID | PMC3335396 |
Grant List | 5T15LM007359 / LM / NLM NIH HHS / United States R33 CA137673 / CA / NCI NIH HHS / United States R33 CA137673 / CA / NCI NIH HHS / United States R33 CA137673-01 / CA / NCI NIH HHS / United States T15 LM007359 / LM / NLM NIH HHS / United States T15 LM007359-01 / LM / NLM NIH HHS / United States |