2007
DOI: 10.1038/sj.onc.1210720
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Stromal inactivation of BMPRII leads to colorectal epithelial overgrowth and polyp formation

Abstract: Stromal-epithelial interactions play a central role in development and tumorigenesis. Bone morphogenetic protein (BMP) signaling in the intestine is involved in both of these processes. Inactivation of BMP pathway genes in the epithelium is known to cause intestinal polyposis. However, the role of the intestinal stroma in polyp initiation is incompletely understood. We observed that conditional inactivation of the BMP type II receptor (BMPRII) in the stroma leads to epithelial hyperplasia throughout the colon … Show more

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Cited by 71 publications
(60 citation statements)
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“…However, different results are seen when BMP signaling is examined in vivo. Disruption of BMPR2, the receptor for BMP2, 4, and 7, leads to epithelial hyperplasia and formation of polyps in the colon (22) and to enhanced metastasis in mice transgenic for MMTV-PyMT (23). Consistent with this, expression of constitutively active BMPR1B in mammary tumor cells suppresses metastasis to lung (24).…”
Section: Introductionsupporting
confidence: 54%
“…However, different results are seen when BMP signaling is examined in vivo. Disruption of BMPR2, the receptor for BMP2, 4, and 7, leads to epithelial hyperplasia and formation of polyps in the colon (22) and to enhanced metastasis in mice transgenic for MMTV-PyMT (23). Consistent with this, expression of constitutively active BMPR1B in mammary tumor cells suppresses metastasis to lung (24).…”
Section: Introductionsupporting
confidence: 54%
“…It could either be a serendipitous finding, or a genuine indication of altered epithelial -mesenchymal interactions within a subset of tumours. In these tumours, hypoxia-driven metabolic and cell biological changes could hypothetically alter the tumour stroma toward an environment that can facilitate cancer progression, along multiple routes, leading to an enhanced proliferation or survival of tumour epithelial cells (Beppu et al, 2008). Under hypoxic conditions, the tumour stroma can select for the propagation of certain subclones of cancer cells that are optimally endowed for tumour progression.…”
Section: Discussionmentioning
confidence: 99%
“…Conditional inactivation of the bone morphogenic protein Type II receptor in the stroma increases the myofibroblast cell population, causing epithelial hyperplasia throughout the colon. 68 Furthermore, loss of TGF-b responsiveness in fibroblast specific protein-1-positive fibroblasts, by conditional inactivation of the TGF-b Type II receptor, resulted in an increase of scatter factor/hepatocyte growth factor (SF/HGF)-secreting stromal fibroblasts causing intraepithelial neoplasia in prostate and invasive squamous cell carcinoma of the forestomach. 69 In another model, lowering Foxf gene dosage by inactivation of the Foxf1 and Foxf2 mesenchymal forkhead transcription factors results in accumulation of Wnt5a secreting a-SMA positive myofibroblasts.…”
Section: Characterization and Origin Of A Myofibroblastmentioning
confidence: 99%