1. ¹Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
2. ²Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
3. ³Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
4. ⁴Anesthesia and Critical Care, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

Correspondence: Dr AM Goldstein, Department of Pediatric Surgery, Massachusetts General Hospital, 55 Fruit St, Warren 1153, Boston, MA 02114, USA. E-mail: agoldstein@partners.org

⁵These two senior authors have contributed equally to this work.

Received 17 May 2007; Revised 27 June 2007; Accepted 4 July 2007; Published online 13 August 2007.

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 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.