Breast Fibroblasts Modulate Early Dissemination, Tumorigenesis, and Metastasis through Alteration of Extracellular Matrix Characteristics 1 2

Department of Pathology and Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.
Neoplasia (New York, N.Y.) (Impact Factor: 4.25). 03/2013; 15(3):249-62. DOI: 10.1593/neo.121950
Source: PubMed


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.

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Available from: Bahram Parvin, May 28, 2015
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    • "In this study, downregulation of miR-200s increased ECM strength and stiffness, dependent on both Fli-1 and TCF12. In contrast to normal mammary fibroblasts, cancer-associated fibroblasts promote dissemination of premalignant mammary epithelial cells and metastasis of malignant epithelial cells [60]. Cellular senescence is associated with aging and characterized by permanent growth arrest and resistance to apoptosis [87,88]. "
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