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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    • "This increased breast density is attributed to increased cellular and extracellular matrix components in the stroma. The cellular changes in cancer-associated stroma include changes in the number and activation of carcinoma-associated fibroblasts [59,60]. The activation of cancer-associated fibroblasts is thought to alter the environment by changing the composition of growth factors and ECM proteins and thereby plays a role in breast cancer development. "
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