Stromal inactivation of BMPRII leads to colorectal epithelial overgrowth and polyp formation.
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 with increased epithelial cell proliferation. Mutant mice developed rectal bleeding and hamartomatous polyps in the colorectum. The polyps demonstrated increased proliferation of epithelial and mesenchymal cells in the mucosa with an expansion of the myofibroblast cell population. These results demonstrate that genetic mutations altering the BMP signaling pathway in the stromal microenvironment can lead to epithelial tumors in the colon.
Beppu
H
H
Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Mwizerwa
O N
ON
Beppu
Y
Y
Dattwyler
M P
MP
Lauwers
G Y
GY
Bloch
K D
KD
Goldstein
A M
AM
D000818:Animals; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002450:Cell Communication / Q000235:genetics; D049109:Cell Proliferation; D003111:Colonic Polyps / Q000378:metabolism / Q000473:pathology*; D006222:Hamartoma / Q000235:genetics / Q000473:pathology; D006965:Hyperplasia / Q000235:genetics / Q000473:pathology; D019426:Integrases / Q000235:genetics; D007381:Intermediate Filament Proteins / Q000235:genetics; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics; D064231:Nestin; D012007:Rectum / Q000473:pathology*; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology
D019485:Bone Morphogenetic Proteins; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D052006:Bone Morphogenetic Protein Receptors, Type II; C045073:Cre recombinase; D019426:Integrases