期刊
MATRIX BIOLOGY
卷 60-61, 期 -, 页码 86-95出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.matbio.2016.08.001
关键词
Breast cancer; Cancer-associated fibroblasts; Extracellular matrix; Fibronectin; Pro-angiogenic signaling
资金
- NSF [DMR-1352299]
- NIH/NCI [R01 CA185293]
- NIH-Biotechnology Resource Center (BRC) [1S10RR025502-01, 1S100D010605-01A1]
- Nanobiotechnology Center (NBTC)
- Division Of Materials Research
- Direct For Mathematical & Physical Scien [1352299] Funding Source: National Science Foundation
Breast cancer cells recruit surrounding stromal cells, such as cancer-associated fibroblasts (CAFs), to remodel their extracellular matrix (ECM) and promote invasive tumor growth. Two. major ECM components, fibronectin (Fn) and collagen I (Col I), are known to interact with each other to regulate cellular behavior. In this study, we seek to understand how Fn and Col I interplay and promote a dysregulated signaling pathway to facilitate tumor progression. Specifically, we investigated the evolution of tumor-conditioned stromal ECM composition, structure, and relaxation. Furthermore, we assessed how evolving Fn-Col I interactions gradually affected pro-angiogenic signaling. Our data first indicate that CAFs initially assembled a strained, viscous, and unfolded Fn matrix. This early altered Fn matrix was later remodeled into a thick Col I-rich matrix that was characteristic of a dense tumor mass. Next, our results suggest that this ECM remodeling was primarily mediated by matrix metalloproteinases (MMPs). This MMP activity caused profound structural and mechanical changes in the developing ECM, which then modified vascular endothelial growth factor (VEGF) secretion by CAFs and matrix sequestration. Collectively, these findings enhance our understanding of the mechanisms by which Fn and Col I synergistically interplay in promoting a sustained altered signaling cascade to remodel the breast tumor stroma for invasive breast tumor growth. (C) 2016 The Authors. Published by Elsevier B.V.
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