Breast fibroblasts modulate early dissemination, tumorigenesis, and metastasis through alteration of extracellular matrix characteristics

Nancy Dumont, Bob Liu, Rosa Anna Defilippis, Hang Chang, Joseph T. Rabban, Anthony Karnezis, Judy A. Tjoe, James Marx, Bahram Parvin, Thea D. Tlsty

Research output: Contribution to journalArticle

77 Scopus citations

Abstract

A wealth of evidence has now demonstrated that the microenvironment in which a tumorigenic cell evolves is as critical to its evolution as the genetic mutations it accrues. However, there is still relatively little known about how signals from the microenvironment contribute to the early events in the progression to malignancy. To address this question, we used a premalignant mammary model to examine how fibroblasts, and the extracellular matrix (ECM) proteins they secrete, influence progression to malignancy. Their effect on metastatic malignant cells was also assessed for comparison. We found that carcinoma-associated fibroblasts, and the distinct aligned ECM they deposit, can cause both premalignant and malignant mammary epithelial cells to assume a mesenchymal morphology that is associated with increased dissemination and metastasis, while benign reduction mammoplasty fibroblasts favor the maintenance of an epithelial morphology and constrain early dissemination, tumor growth, and metastasis. Our results suggest that normalizing the organization of the ECM could be effective in limiting systemic dissemination and tumor growth.

Original languageEnglish (US)
Pages (from-to)249-262
Number of pages14
JournalNeoplasia (United States)
Volume15
Issue number3
DOIs
StatePublished - Jan 1 2013
Externally publishedYes

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ASJC Scopus subject areas

  • Cancer Research

Cite this

Dumont, N., Liu, B., Defilippis, R. A., Chang, H., Rabban, J. T., Karnezis, A., Tjoe, J. A., Marx, J., Parvin, B., & Tlsty, T. D. (2013). Breast fibroblasts modulate early dissemination, tumorigenesis, and metastasis through alteration of extracellular matrix characteristics. Neoplasia (United States), 15(3), 249-262. https://doi.org/10.1593/neo.121950