Cancer-associated fibroblasts promote proliferation, angiogenesis, metastasis and immunosuppression in gastric cancer

Matrix Biol. 2024 Sep:132:59-71. doi: 10.1016/j.matbio.2024.06.004. Epub 2024 Jun 25.

Abstract

Despite advances in surgery, radiotherapy and immunotherapy, the mortality rate for gastric cancer remains one of the highest in the world. A large body of evidence has demonstrated that cancer-associated fibroblasts (CAFs), as core members of the stroma, can secrete cytokines, proteins and exosomes to create a tumour microenvironment that is conducive to cancer cell survival. CAFs can also interact with cancer cells to form a complex signalling network, enabling cancer cells to more easily metastasise to other organs and tissues in the body and develop metastatic foci. In this review, we provide an overview of the CAFs concept and activators. We focus on elucidating their effects on immune cells, intratumoural vasculature, extracellular matrix, as well as cancer cell activity, metastatic power and metabolism, and on enhancing the metastatic ability of cancer cells through activation of JAK/STAT, NF/κB and CXCL12/CXCR4. Various therapeutic agents targeting CAFs are also under development and are expected to improve the prognosis of gastric cancer in combination with existing treatment options.

Keywords: Cancer-associated fibroblasts; Cytokines; Gastric cancer; Metastasis; Therapeutic target.

Publication types

  • Review

MeSH terms

  • Animals
  • Cancer-Associated Fibroblasts* / metabolism
  • Cancer-Associated Fibroblasts* / pathology
  • Cell Proliferation
  • Chemokine CXCL12 / genetics
  • Chemokine CXCL12 / metabolism
  • Humans
  • Neoplasm Metastasis
  • Neovascularization, Pathologic* / metabolism
  • Neovascularization, Pathologic* / pathology
  • Signal Transduction*
  • Stomach Neoplasms* / blood supply
  • Stomach Neoplasms* / immunology
  • Stomach Neoplasms* / metabolism
  • Stomach Neoplasms* / pathology
  • Tumor Microenvironment*

Substances

  • Chemokine CXCL12
  • CXCL12 protein, human