Extracellular Matrix Remodeling and Stiffening Modulate Tumor Phenotype and Treatment Response

Jennifer L. Leight; Allison P. Drain; Valerie M. Weaver

doi:10.1146/annurev-cancerbio-050216-034431

Annual Review of Cancer Biology

Volume 1, 2017

Review Article

Free

Extracellular Matrix Remodeling and Stiffening Modulate Tumor Phenotype and Treatment Response

Jennifer L. Leight¹, Allison P. Drain², and Valerie M. Weaver³
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Affiliations: ¹Department of Biomedical Engineering and The James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210; email: [email protected] ²University of California, Berkeley–University of California, San Francisco Graduate Program in Bioengineering, Center for Bioengineering and Tissue Regeneration, Department of Surgery, University of California, San Francisco, California 94143; email: [email protected] ³Center for Bioengineering and Tissue Regeneration, Department of Surgery, Department of Anatomy, Department of Bioengineering and Therapeutic Sciences, Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, and Helen Diller Comprehensive Cancer Center, University of California, San Francisco, California 94143; email: [email protected]
Vol. 1:313-334 (Volume publication date March 2017) https://doi.org/10.1146/annurev-cancerbio-050216-034431
First published as a Review in Advance on November 09, 2016
© Annual Reviews

Abstract

Solid tumors are characterized by a remodeled and stiffened extracellular matrix. The extracellular matrix is not a passive by-product of the tumor, but actively compromises tissue-specific differentiation, enhances tumor cell proliferation and survival, and fosters tumor cell invasion and migration. The tumor extracellular matrix also influences the behavior of the stromal cells, which through vicious, feedforward-reinforcing pathways promote tumor progression and compromise treatment efficacy. To investigate how the tumor extracellular matrix alters cancer phenotype and treatment, a number of three-dimensional, organotypic culture models have been developed that employ a variety of materials, including natural matrices, collagen, fibrin, and reconstituted basement membrane gels, as well as synthetic hydrogel materials such as polyacrylamide and polyethylene glycol. These models have been used to interrogate how specific microenvironmental features modify tumor and stromal cell function and to identify the molecular mechanisms that regulate tumorigenesis and therapeutic efficacy. To translate these findings into more effective treatment strategies for patients, clinically informed studies are needed that incorporate computational modeling and in vivo validation.

Keyword(s): cancer, extracellular matrix, remodeling, tissue stiffness, tumor microenvironment

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2017-03-06

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