Phagocyte—extracellular matrix crosstalk empowers tumor development and dissemination

Chen Varol*, Irit Sagi

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

Abstract

Phagocytes, such as tumor-associated macrophages (TAMs) and tumor-associated neutrophils (TANs), are abundant in the stroma of experimental and human tumors and are locally educated to mediate important biological functions that profoundly affect tumor initiation, growth, and dissemination. Of considerable importance is the noncellular component of the tumor microenvironment, namely—the extracellular matrix (ECM). This milieu is often overlooked due to its complexity and vast heterogeneity. Biophysical and biomechanical cues provided by the dynamically evolving tumorigenic ECM fundamentally modulate every behavioral facet of the cancer cells and of associated stromal cells. In this review, we discuss the intricate interplay between phagocytes and ECM that are lined up to support tumor progression. TAMs and TANs shape the tumorigenic ECM by providing key matrix-remodeling enzymes and structural proteins and in turn, the altered tumor ECM modulates their migration and function. A better mechanistic comprehension of this reciprocal dependence has exciting implications for the development of new therapeutic options for cancer.

Original languageEnglish
Pages (from-to)734-751
Number of pages18
JournalFEBS Journal
Volume285
Issue number4
DOIs
StatePublished - Feb 2018

Keywords

  • extracellular matrix
  • matrix metalloproteinases
  • tumor microenvironment
  • tumor-associated macrophages
  • tumor-associated neutrophils

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