Department of Biomedical Engineering and Wisconsin Institute for Medical Research, University of Wisconsin-Madison, Madison, Wisconsin 53705, USA.
Integr Biol (Camb). 2012 Feb;4(2):142-52. doi: 10.1039/c1ib00104c. Epub 2012 Jan 11.
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.
尽管有强有力的证据表明基质在 Hedgehog 信号中起作用，但对于基质细胞的身份以及介导 Hh 信号促进生长的信号机制知之甚少。我们使用微通道技术开发了一种体外共培养模型，用于研究旁分泌 Hh 信号对前列腺癌细胞增殖的影响。我们在这里表明，肌成纤维细胞中 Hh 信号的激活足以加速肿瘤细胞的生长。这种效应不依赖于 Hh 配体对肿瘤细胞或肿瘤基质的其他细胞成分的任何直接影响。此外，肌成纤维细胞中 Hh 通路激活的营养作用不需要基质的其他成分的协作，也不需要与癌细胞的直接物理相互作用。通过分离前列腺基质中 Hh 通路激活的营养作用，我们朝着确定介导旁分泌 Hh 信号对肿瘤生长影响的细胞特异性机制迈出了第一步。
