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

Tanuka Biswas, Xiang Gu, Junhua Yang, Lesley G. Ellies, Lu Zhe Sun

Research output: Contribution to journalArticle

19 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)129-138
Number of pages10
JournalCancer Letters
Volume346
Issue number1
DOIs
StatePublished - Apr 28 2014

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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