Pancreatic cancer, stroma, and exosomes

Abstract

In the pathogenesis of pancreatic adenocarcinoma, tumor stroma plays a key role in both aggressiveness, immune evasion, resistance to chemotherapy, and the ability to metastasize. Among the elements that characterize the behavior of the stroma, extracellular vesicles and, in particular, exosomes play an important role. These extracellular vesicles carry a wide range of bioactive molecules, from transcription factors to microRNAs, which can substantially alter the phenotype of the cellular components of the stroma. Exosomes are involved in the exchange of signals between tumor cells, tumor-associated macrophages, cancer-associated fibroblasts, and also with the healthy cells surrounding the tumor. They can transfer resistance to chemotherapeutic drugs, promote the epithelial-mesenchymal transition, modify the phenotype of macrophages, or induce the expression of molecules that alter the extracellular matrix to facilitate migration and metastasis. On the other hand, all these characteristics make these vesicles first-rate therapeutic targets, as controlling their functionality could greatly enhance the effectiveness of treatments that, today, are still far from be satisfactory.

Keywords: CAF; Exosomes; Extracellular vesicles; Pancreatic cancer; Stroma; TAM.

Fig. 1

Exosomes are involved in the interactions between all the cell types present in the pancreatic tumor stroma. Interactions include the transfer of enzymes, signaling proteins, RNA, miRNA, and fragments of DNA. TAM, tumor-associated macrophages; CAF, cancer-associated fibroblasts; PDAC, pancreatic ductal adenocarcinoma