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- Title
Restoring TGFβ function in microsatellite unstable (MSI-H) colorectal cancer reduces tumourigenicity but increases metastasis formation.
- Authors
Warusavitarne, Janindra; McDougall, Fiona; de Silva, Keshani; Barnetson, Rebecca; Messina, Marinella; Robinson, Bruce G.; Schnitzler, Margaret
- Abstract
TGFβ is an important cell growth regulator which may have a role in metastasis formation. Microsatellite unstable (MSI-H) colon cancer serves as a unique model to demonstrate this as most MSI-H colon cancers have a mutation in the transforming growth factor beta receptor II ( TGFβRII) gene and a low metastatic rate. To demonstrate an increase in invasion and metastasis in a MSI-H colorectal cancer cell line with a known mutation in TGFβRII. By restoring the wild-type TGFβRII gene in the KM12C MSI-H colorectal carcinoma cell line with a known mutation in TGFβRII, we have demonstrated that both invasion and metastasis in this cell line was significantly increased. A mouse metastatic model have shown that liver metastases were increased in mice inoculated with cells containing a wild-type TGFβRII gene (42% for the transfected group compared with 15% for the control group; p = 0.0379), despite a reduction in the size of primary tumours. This study highlights an important mechanism which may contribute to the low metastatic rate of MSI-H colon cancers and demonstrates the importance of TGFβ signalling in metastasis formation. Previous studies involving breast cancer cell lines have shown that blocking TGFβ signalling results in a reduction in metastasis formation. This study is the first study to use a cell line with a low metastatic rate and TGFβRII mutations to demonstrate that restoring TGFβ signalling increases the metastatic rate.
- Subjects
CELL growth; METASTASIS; COLON cancer; GROWTH regulators; TRANSFORMING growth factors-beta; CELL lines
- Publication
International Journal of Colorectal Disease, 2009, Vol 24, Issue 2, p139
- ISSN
0179-1958
- Publication type
Article
- DOI
10.1007/s00384-008-0606-x