Crosstalk between Pancreatic Cancer Cells and Cancer-Associated Fibroblasts in the Tumor Microenvironment Mediated by Exosomal MicroRNAs

Int J Mol Sci. 2022 Aug 23;23(17):9512. doi: 10.3390/ijms23179512.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant digestive tumors, characterized by a low rate of early diagnosis, strong invasiveness, and early metastasis. The abundant stromal cells, dense extracellular matrix, and lack of blood supply in PDAC limit the penetration of chemotherapeutic drugs, resulting in poor efficacy of the current treatment regimens. Cancer-associated fibroblasts (CAFs) are the major stromal cells in the tumor microenvironment. Tumor cells can secrete exosomes to promote the generation of activated CAFs, meanwhile exosomes secreted by CAFs help promote tumor progression. The aberrant expression of miRNAs in exosomes is involved in the interaction between tumor cells and CAFs, which provides the possibility for the application of exosomal miRNAs in the diagnosis and treatment of PDAC. The current article reviews the mechanism of exosomal miRNAs in the crosstalk between PDAC cells and CAFs in the tumor microenvironment, in order to improve the understanding of TME regulation and provide evidence for designing diagnostic and therapeutic targets against exosome miRNA in human PDAC.

Keywords: PDAC; cancer-associated fibroblasts; exosomal miRNAs; tumor microenvironment.

Publication types

  • Review

MeSH terms

  • Cancer-Associated Fibroblasts* / metabolism
  • Carcinoma, Pancreatic Ductal* / pathology
  • Cell Line, Tumor
  • Exosomes* / metabolism
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Pancreatic Neoplasms* / pathology
  • Tumor Microenvironment / genetics

Substances

  • MicroRNAs

Grants and funding

This study was supported by The National Natural Science Foundation of China (NO. 81672353 and 81871954) and Beijing Municipal Natural Science Foundation (NO. 7212111).