UC San Diego
Attenuation of TGF-β signaling supports tumor progression of a mesenchymal-like mammary tumor cell line in a syngeneic murine model
- Author(s): Biswas, T
- Gu, X
- Yang, J
- Ellies, LG
- Sun, LZ
- et al.
Published Web Locationhttp://www.cancerletters.info/article/S0304-3835(13)00856-2/abstract
Previous studies have suggested that TGF-β functions as a tumor promoter in metastatic, mesenchymal-like breast cancer cells and that TGF-β 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-β receptor II (TβRII) 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-β 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-β signaling in mesenchymal-like mammary tumors does not necessarily inhibit their malignant potential, and anti-TGF-β therapeutic intervention requires greater precision in identifying molecular markers in tumors with an indication of functional TGF-β signaling. © 2013 Elsevier Ireland Ltd.
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