title: 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.
authors.affiliation: Department of Biomedical Engineering and Wisconsin Institute for Medical Research, University of Wisconsin-Madison, Madison, Wisconsin 53705, USA.
authors.forename: Maribella
authors.initials: M
authors.lastname: Domenech
authors.forename: Robert
authors.initials: R
authors.lastname: Bjerregaard
authors.forename: Wade
authors.initials: W
authors.lastname: Bushman
authors.forename: David J
authors.initials: DJ
authors.lastname: Beebe
mesh_terms: D002454:Cell Differentiation / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D018920:Coculture Techniques / Q000379:methods; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008856:Microscopy, Fluorescence; D058628:Myofibroblasts / Q000378:metabolism* / Q000473:pathology; D019899:Paracrine Communication; D000072079:Patched Receptors; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D012313:RNA / Q000737:chemistry / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000071676:Zinc Finger Protein GLI1
chemical_list: C400551:GLI1 protein, human; D053823:Hedgehog Proteins; D000072079:Patched Receptors; D011956:Receptors, Cell Surface; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1; D012313:RNA