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

TitleBreast fibroblasts modulate early dissemination, tumorigenesis, and metastasis through alteration of extracellular matrix characteristics
Publication TypeJournal Article
Year of Publication2013
AuthorsDumont N, Liu B, DeFilippis RAnna, Chang H, Rabban JT, Karnezis AN, Tjoe JA, Marx J, Parvin B, Tlsty TD
JournalNeoplasia
Volume15
Issue3
Pagination249-62
Date Published2013 Mar
ISSN1476-5586
KeywordsAnimals, Breast, Cell Line, Tumor, Cell Transformation, Neoplastic, Coculture Techniques, Epithelial Cells, Extracellular Matrix, Extracellular Signal-Regulated MAP Kinases, Female, Fibroblasts, Humans, Lung Neoplasms, Mammary Neoplasms, Experimental, Neoplasm Metastasis, Phenotype, Proto-Oncogene Proteins c-jun, rho GTP-Binding Proteins, Signal Transduction, Transforming Growth Factor beta
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.

Alternate JournalNeoplasia
PubMed ID23479504
PubMed Central IDPMC3593149
Grant ListNIH/NCI R01 CA097214 / CA / NCI NIH HHS / United States
NIH/NCI U54 CA143803 / CA / NCI NIH HHS / United States
P01 CA107584 / CA / NCI NIH HHS / United States
P01 CA107584 / CA / NCI NIH HHS / United States
R01 CA097214 / CA / NCI NIH HHS / United States
U54 CA143803 / CA / NCI NIH HHS / United States