Attenuation of TGF-beta signaling supports tumor progression of a mesenchymal-like mammary tumor cell line in a syngeneic murine model

作者：Biswas Tanuka; Gu Xiang; Yang Junhua; Ellies Lesley G; Sun Lu Zhe^*

来源：Cancer Letters, 2014, 346(1): 129-138.

DOI：10.1016/j.canlet.2013.12.018

• TGF-beta
• MMTV-PyMT mammary tumor
• Syngeneic model
• Metastasis

Previous studies have suggested that TGF-beta functions as a tumor promoter in metastatic, mesenchymal-like breast cancer cells and that TGF-beta inhibitors can effectively abrogate tumor progression in several of these models. Here we report a novel observation with the use of genetic and pharmacological approaches, and murine mammary cell injection models in both syngeneic and immune compromised mice. We found that TGF-beta receptor II (T beta RII) knockdown in the MMTV-PyMT derived Py8119, a mesenchymal-like murine mammary tumor cell line, resulted in increased orthotopic tumor growth potential in a syngeneic background and a similar trend in an immune compromised background. Systemic treatment with a small-molecule TGF-beta receptor I kinase inhibitor induced a trend towards increased metastatic colonization of distant organs following intracardiac inoculation of Py8119 cells, with little effect on the colonization of luminal-like Py230 cells, also derived from MMTV-PyMT tumors. Taken together, our data suggest that the attenuation of TGF-beta signaling in mesenchymal-like mammary tumors does not necessarily inhibit their malignant potential, and anti-TGF-beta therapeutic intervention requires greater precision in identifying molecular markers in tumors with an indication of functional TGF-beta signaling.

• 出版日期2014-4-28