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

Authors
  • Biswas, Tanuka
  • Gu, Xiang
  • Yang, Junhua
  • Ellies, Lesley G.
  • Sun, Lu-Zhe1, 2, 3, 4, 5, 2
  • 1 Department of Cellular and Structural Biology
  • 2 University of Texas Health Science Center at San Antonio
  • 3 Department of Pathology
  • 4 University of California at San Diego
  • 5 Cancer Therapy and Research Center
Type
Published Article
Journal
Cancer Letters
Publisher
Elsevier
Publication Date
Jan 01, 2013
Accepted Date
Dec 14, 2013
Volume
346
Issue
1
Pages
129–138
Identifiers
DOI: 10.1016/j.canlet.2013.12.018
Source
Elsevier
Keywords
License
Unknown

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.

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