Modeling the tumor extracellular matrix: Tissue engineering tools repurposed towards new frontiers in cancer biology

TitleModeling the tumor extracellular matrix: Tissue engineering tools repurposed towards new frontiers in cancer biology
Publication TypeJournal Article
Year of Publication2014
AuthorsGill, BJ, West, JL
JournalJ Biomech
Volume47
Issue9
Pagination1969–1978
Date Published06/2014
ISSN00219290
Keywordsextracellular matrix; hydrogels; Mechanotransduction; Metastasis; poly(ethylene glycol); Synthetic scaffold; Tissue Engineering; Tumor microenvironment
Abstract

Cancer progression is mediated by complex epigenetic, protein and structural influences. Critical among them are the biochemical, mechanical and architectural properties of the extracellular matrix (ECM). In recognition of the ECM's important role, cancer biologists have repurposed matrix mimetic culture systems first widely used by tissue engineers as new tools for in vitro study of tumor models. In this review we discuss the pathological changes in tumor ECM, the limitations of 2D culture on both traditional and polyacrylamide hydrogel surfaces in modeling these characteristics and advances in both naturally derived and synthetic scaffolds to facilitate more complex and controllable 3D cancer cell culture. Studies using naturally derived matrix materials like Matrigel and collagen have produced significant findings related to tumor morphogenesis and matrix invasion in a 3D environment and the mechanotransductive signaling that mediates key tumor-matrix interaction. However, lack of precise experimental control over important matrix factors in these matrices have increasingly led investigators to synthetic and semi-synthetic scaffolds that offer the engineering of specific ECM cues and the potential for more advanced experimental manipulations. Synthetic scaffolds composed of poly(ethylene glycol) (PEG), for example, facilitate highly biocompatible 3D culture, modular bioactive features like cell-mediated matrix degradation and complete independent control over matrix bioactivity and mechanics. Future work in PEG or similar reductionist synthetic matrix systems should enable the study of increasingly complex and dynamic tumor-ECM relationships in the hopes that accurate modeling of these relationships may reveal new cancer therapeutics targeting tumor progression and metastasis.

DOI10.1016/j.jbiomech.2013.09.029
Short TitleJournal of Biomechanics
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