Hyaluronan, cancer-associated fibroblasts and the tumor microenvironment in malignant progression

James B. McCarthy, Dorraya El-Ashry, Eva A. Turley

Research output: Contribution to journalReview article

28 Scopus citations

Abstract

This review summarizes the roles of CAFs in forming a "cancerized" fibrotic stroma favorable to tumor initiation and dissemination, in particular highlighting the functions of the extracellular matrix component hyaluronan (HA) in these processes. The structural complexity of the tumor and its host microenvironment is now well appreciated to be an important contributing factor to malignant progression and resistance-to-therapy. There are multiple components of this complexity, which include an extensive remodeling of the extracellular matrix (ECM) and associated biomechanical changes in tumor stroma. Tumor stroma is often fibrotic and rich in fibrillar type I collagen and hyaluronan (HA). Cancer-associated fibroblasts (CAFs) are a major source of this fibrotic ECM. CAFs organize collagen fibrils and these biomechanical alterations provide highways for invading carcinoma cells either under the guidance of CAFs or following their epithelial to mesenchymal transition (EMT). The increased HA metabolism of a tumor microenvironment instructs carcinoma initiation and dissemination by performing multiple functions. The key effects of HA reviewed here are its role in activating CAFs in pre-malignant and malignant stroma, and facilitating invasion by promoting motility of both CAFs and tumor cells, thus facilitating their invasion. Circulating CAFs (cCAFs) also form heterotypic clusters with circulating tumor cells (CTC), which are considered to be pre-cursors of metastatic colonies. cCAFs are likely required for extravasation of tumors cells and to form a metastatic niche suitable for new tumor colony growth. Therapeutic interventions designed to target both HA and CAFs in order to limit tumor spread and increase response to current therapies are discussed.

Original languageEnglish (US)
Article number48
JournalFrontiers in Cell and Developmental Biology
Volume6
Issue numberMAY
DOIs
StatePublished - May 8 2018

Keywords

  • Cancer-associated fibroblasts
  • Circulating cancer-associated fibroblasts
  • Hyaluronan
  • Metastasis
  • Migration
  • Tumor initiation
  • Tumor microenvironment

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Hyaluronan, cancer-associated fibroblasts and the tumor microenvironment in malignant progression'. Together they form a unique fingerprint.

  • Cite this