The Extracellular Matrix Modulates the Metastatic Journey

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

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