BMP pathway suppression is an early event in inflammation-driven colon neoplasmatogenesis of uPA-deficient mice
| Autor: | Theofilos Poutahidis, Hara Afaloniati, Elisavet Karamanavi, George S. Karagiannis, Katerina Angelopoulou |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Adenoma Pathology medicine.medical_specialty animal structures Colorectal cancer Adenocarcinoma Bone morphogenetic protein Real-Time Polymerase Chain Reaction 03 medical and health sciences Mice 0302 clinical medicine Downregulation and upregulation medicine Animals Noggin Receptor Inflammation business.industry General Medicine medicine.disease Urokinase-Type Plasminogen Activator digestive system diseases BMPR2 Disease Models Animal 030104 developmental biology Cell Transformation Neoplastic 030220 oncology & carcinogenesis embryonic structures Bone Morphogenetic Proteins Colonic Neoplasms Cancer research Signal transduction Chordin business Precancerous Conditions Signal Transduction |
| Zdroj: | Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. 37(2) |
| ISSN: | 1423-0380 |
| Popis: | The suppression of the bone morphogenetic protein (BMP) signaling pathway has been recently shown to promote adenoma-to-carcinoma transition in sporadic colon cancer. However, its role in the evolution of early preneoplastic changes to neoplasia remains elusive. In the present study, we aimed to investigate the gene expression levels of multiple extracellular BMP family constituents, including BMP ligands/receptors and inhibitors, during the early stages of inflammation-associated colon carcinogenesis. For that, we used the recently developed urokinase-type plasminogen activator (uPA)-deficient mouse model of colonic polypoidogenesis, in which adenomatous polyps arise several months after the induction of dextran sodium sulfate (DSS) colitis. In DSS-treated wild-type mice, the preneoplastic lesions which did not eventually evolve to adenomas resided in a colitic microenvironment characterized by a balanced upregulation of both BMP ligands, i.e., Bmp4/7 and BMP inhibitors, such as chordin, noggin, and gremlin-1. In the uPA-deficient tumor-promoting inflammatory microenvironment, however, there was a clear evidence for BMP pathway suppression. By contrast to DSS-treated wild-type controls, the inflammation-associated Bmp4 upregulation was abolished, and the BMP signaling suppression was further enhanced by a particularly high increase of gremlin-1 expression. These findings propose that BMP pathway suppression in colon cancer could be associated with very early stages of the preneoplasia-to-neoplasia sequence of events. |
| Databáze: | OpenAIRE |
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