Roles of TGF-β signals in tumor microenvironment via regulation of the formation and plasticity of vascular system

Semin Cancer Biol. 2023 Jul:92:130-138. doi: 10.1016/j.semcancer.2023.04.007. Epub 2023 Apr 15.

Abstract

Tumor cells evolve in tumor microenvironment composed of multiple cell types. Among these, endothelial cells (ECs) are the major players in tumor angiogenesis, which is a driver of tumor progression and metastasis. Increasing evidence suggests that ECs also contribute to tumor progression and metastasis as they modify their phenotypes to differentiate into mesenchymal cells through a process known as endothelial-mesenchymal transition (EndoMT). This plasticity of ECs is mediated by various cytokines, including transforming growth factor-β (TGF-β), and modulated by other stimuli depending on the cellular contexts. Recent lines of evidence have shown that EndoMT is involved in various steps of tumor progression, including tumor angiogenesis, intravasation and extravasation of cancer cells, formation of cancer-associated fibroblasts, and cancer therapy resistance. In this review, we summarize current updates on EndoMT, highlight the roles of EndoMT in tumor progression and metastasis, and underline targeting EndoMT as a potential therapeutic strategy.

Keywords: Cancer therapy resistance; EMT; EndoMT; Metastasis; TGF-β; Tumor angiogenesis; Tumor microenvironment.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cytokines / metabolism
  • Endothelial Cells* / metabolism
  • Endothelium
  • Epithelial-Mesenchymal Transition / genetics
  • Humans
  • Neovascularization, Pathologic / metabolism
  • Transforming Growth Factor beta* / metabolism
  • Tumor Microenvironment / genetics

Substances

  • Transforming Growth Factor beta
  • Cytokines