Journal
TRENDS IN BIOTECHNOLOGY
Volume 33, Issue 4, Pages 230-236Publisher
ELSEVIER SCIENCE LONDON
DOI: 10.1016/j.tibtech.2015.01.004
Keywords
desmoplasia; extracellular matrix; Rho-ROCK; integrins; biomechanical and biochemical cues; cell-ECM dynamic reciprocity
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Funding
- Temple-Fox Chase Cancer Center (FCCC) Nodal Multi-PI Grant (PIL/EC)
- National Institutes of Health (NIH) National Cancer Institute (NCI) [R01 CA113451]
- Greenberg Family
- Bucks County Board of Associates
- FCCC Pancreatic Cancer Research
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The extracellular matrix (ECM) provides structural and biochemical signals that regulate cell function. A well-controlled balance between cells and surroundings (i.e., dynamic reciprocity) is crucial for regulating ECM architecture. During cancer progression, epithelial cells undergo genetic alterations which, together with stromal changes including ECM remodeling, disturb the homeostatic dynamics of the epithelium. A parallel organization of stromal ECM fibrils is associated with tumorigenic responses. In an emerging paradigm, continuous and progressive regulation via mechanical forces and aberrant signaling are believed to be responsible for tumor-associated ECM remodeling. In this review we discuss the discrete biomechanical and biochemical mechanisms that underlie these architectural changes and highlight their particular relevance to the regulation of the alignment of ECM in the mesenchymal stroma.
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