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Stromal EGF and igf-I together modulate plasticity of disseminated triple-negative breast tumors

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Author

  • Zafira Castaño
  • Timothy Marsh
  • Ramya Tadipatri
  • Hanna S Kuznetsov
  • Fatima Al-Shahrour
  • Mahnaz Paktinat
  • April Greene-Colozzi
  • Björn Nilsson
  • Andrea L Richardson
  • Sandra S McAllister

Summary, in English

The causes for malignant progression of disseminated tumors and the reasons recurrence rates differ in women with different breast cancer subtypes are unknown. Here, we report novel mechanisms of tumor plasticity that are mandated by microenvironmental factors and show that recurrence rates are not strictly due to cell-intrinsic properties. Specifically, outgrowth of the same population of incipient tumors is accelerated in mice with triple-negative breast cancer (TNBC) relative to those with luminal breast cancer. Systemic signals provided by overt TNBCs cause the formation of a tumor-supportive microenvironment enriched for EGF and insulin-like growth factor-I (IGF-I) at distant indolent tumor sites. Bioavailability of EGF and IGF-I enhances the expression of transcription factors associated with pluripotency, proliferation, and epithelial-mesenchymal transition. Combinatorial therapy with EGF receptor and IGF-I receptor inhibitors prevents malignant progression. These results suggest that plasticity and recurrence rates can be dictated by host systemic factors and offer novel therapeutic potential for patients with TNBC.

Department/s

Publishing year

2013-08

Language

English

Pages

922-935

Publication/Series

Cancer Discovery

Volume

3

Issue

8

Document type

Journal article

Publisher

American Association for Cancer Research

Topic

  • Cancer and Oncology

Keywords

  • Animals
  • Antineoplastic Agents
  • Cell Line, Tumor
  • Cell Proliferation
  • Disease Progression
  • Epidermal Growth Factor
  • Epithelial-Mesenchymal Transition
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Insulin-Like Growth Factor I
  • Mice
  • Mice, Nude
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local
  • Neoplasm Transplantation
  • Receptor, Epidermal Growth Factor
  • Receptor, IGF Type 1
  • Stromal Cells
  • Transcription Factors
  • Triple Negative Breast Neoplasms
  • Tumor Microenvironment
  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

Status

Published

Research group

  • Hematogenomics

ISBN/ISSN/Other

  • ISSN: 2159-8274