The Extracellular Matrix Modulates the Metastatic Journey

FuiBoon Kai; Allison P Drain; Valerie M Weaver

doi:10.1016/j.devcel.2019.03.026

The Extracellular Matrix Modulates the Metastatic Journey

Dev Cell. 2019 May 6;49(3):332-346. doi: 10.1016/j.devcel.2019.03.026.

Authors

FuiBoon Kai¹, Allison P Drain², Valerie M Weaver³

Affiliations

¹ Center for Bioengineering and Tissue Regeneration, Department of Surgery, University of California, San Francisco, San Francisco, CA, USA.
² Center for Bioengineering and Tissue Regeneration, Department of Surgery, University of California, San Francisco, San Francisco, CA, USA; University of California Berkeley/University of California San Francisco Graduate Program in Bioengineering, San Francisco, CA, USA.
³ Center for Bioengineering and Tissue Regeneration, Department of Surgery, University of California, San Francisco, San Francisco, CA, USA; Departments of Radiation Oncology and Bioengineering and Therapeutic Sciences, Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, and UCSF Helen Diller Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA. Electronic address: valerie.weaver@ucsf.edu.

Abstract

The extracellular matrix is perturbed in tumors. The tumor matrix promotes the growth, survival, and invasion of the cancer and modifies fibroblast and immune cell behavior to drive metastasis and impair treatment. Here, we discuss how the tumor matrix regulates metastasis by fostering tumor cell invasion into the stroma and migration toward the vasculature. We describe the role of the tumor matrix in cancer cell intravasation and vascular dissemination. We examine the impact of the matrix on disseminated tumor cell extravasation and on tumor dormancy and metastatic outgrowth. Finally, we discuss the clinical outcome of therapeutics that normalize tumor-matrix interactions.

Keywords: angiogenesis; dormancy; extracellular matrix; extravasation; integrin; intravasation; invasion; mechanics; mechanotransduction; metastasis; migration; outgrowth; pre-metastatic niche; tissue tension.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Review

MeSH terms

Animals
Extracellular Matrix / metabolism
Extracellular Matrix / pathology*
Fibroblasts / metabolism
Humans
Neoplasm Invasiveness / pathology
Neoplasm Metastasis / pathology*
Neoplasms / metabolism
Neoplasms / pathology*
Neovascularization, Pathologic / pathology

Abstract

Publication types

MeSH terms

Grants and funding