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J Clin Invest. 2018 Jan 2;128(1):16-25. doi: 10.1172/JCI93554. Epub 2018 Jan 2.

The fibrotic tumor stroma.

Author information

1
Oral and Craniofacial Health Sciences, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
2
Department of Biomedical Engineering, School of Engineering and Applied Sciences and School of Medicine, University of Virginia, Charlottesville, Virginia, USA.
3
Department of Thoracic/Head and Neck Medical Oncology and.
4
Department of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Abstract

Intratumoral fibrosis results from the deposition of a cross-linked collagen matrix by cancer-associated fibroblasts (CAFs). This type of fibrosis has been shown to exert mechanical forces and create a biochemical milieu that, together, shape intratumoral immunity and influence tumor cell metastatic behavior. In this Review, we present recent evidence that CAFs and tumor cells are regulated by provisional matrix molecules, that metastasis results from a change in the type of stromal collagen cross-link, and that fibrosis and inflammation perpetuate each other through proteolytic and chemotactic mediators released into the tumor stroma. We also discuss aspects of the emerging biology that have potential therapeutic value.

PMID:
29293090
PMCID:
PMC5749516
DOI:
10.1172/JCI93554
[Indexed for MEDLINE]
Free PMC Article

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