Cancer-associated fibroblasts produce matrix-bound vesicles that influence endothelial cell function

Sci Signal. 2024 Mar 12;17(827):eade0580. doi: 10.1126/scisignal.ade0580. Epub 2024 Mar 12.

Abstract

Intercellular communication between different cell types in solid tumors contributes to tumor growth and metastatic dissemination. The secretome of cancer-associated fibroblasts (CAFs) plays major roles in these processes. Using human mammary CAFs, we showed that CAFs with a myofibroblast phenotype released extracellular vesicles that transferred proteins to endothelial cells (ECs) that affected their interaction with immune cells. Mass spectrometry-based proteomics identified proteins transferred from CAFs to ECs, which included plasma membrane receptors. Using THY1 as an example of a transferred plasma membrane-bound protein, we showed that CAF-derived proteins increased the adhesion of a monocyte cell line to ECs. CAFs produced high amounts of matrix-bound EVs, which were the primary vehicles of protein transfer. Hence, our work paves the way for future studies that investigate how CAF-derived matrix-bound EVs influence tumor pathology by regulating the function of neighboring cancer, stromal, and immune cells.

MeSH terms

  • Cancer-Associated Fibroblasts* / metabolism
  • Cell Line
  • Cell Line, Tumor
  • Cell Membrane
  • Endothelial Cells
  • Fibroblasts / metabolism
  • Humans
  • Neoplasms* / metabolism
  • Tumor Microenvironment