Extracellular vesicles in pancreatic cancer progression and therapies

Abstract

Pancreatic cancer (PC) is one of the leading causes of cancer-related death worldwide due to delayed diagnosis and limited treatments. More than 90% of all pancreatic cancers are pancreatic ductal adenocarcinoma (PDAC). Extensive communication between tumour cells and other cell types in the tumour microenvironment have been identified which regulate cancer hallmarks during pancreatic tumorigenesis via secretory factors and extracellular vesicles (EVs). The EV-capsuled factors not only facilitate tumour growth locally, but also enter circulation and reach distant organs to construct a pre-metastatic niche. In this review, we delineate the key factors in pancreatic ductal adenocarcinoma derived EVs that mediate different tumour processes. Also, we highlight the factors that are related to the crosstalk with cancer stem cells/cancer-initiating cells (CSC/CIC), the subpopulation of cancer cells that can efficiently metastasize and resist currently used chemotherapies. Lastly, we discuss the potential of EV-capsuled factors in early diagnosis and antitumour therapeutic strategies.

Exploring the Clinical Utility of Pancreatic Cancer Circulating Tumor Cells

“…Isolation methods for exosomes, such as ultracentrifugation are currently inefficient and inconsistent, leading to difficulties in their characterization [37]. However, their clinical applicability as a biomarker in PDAC will continue to grow as well as their therapeutic applications as a delivery system [38,39].…”

The immunoregulation effect of tumor microenvironment in pancreatic ductal adenocarcinoma

“…In TME, pre-metastatic niche formation relies on EVs for extensive communication between tumor cells and others. The EV-capsuled factors not only enter circulation and reach distant organs to construct a pre-metastatic niche, but also facilitate tumor growth locally, include regulating angiogenesis, cellular metabolism, metastasis, cell survival, immune regulation and therapeutic resistance ( 120 ). At the level of gene expression, Rab27a GTPase is overexpressed in advanced tumors during the establishment of pre-metastatic niche and is used to regulate vesicle transport, which is related to the non-cellular autonomous control of tumor growth and metastasis.…”

Cancer-derived small extracellular vesicles: emerging biomarkers and therapies for pancreatic ductal adenocarcinoma diagnosis/prognosis and treatment

“…[30] sEVs derived from cancer cells played a crucial role in PDAC biology, including tumorigenesis, cancer progression, cancer metastasis, immune regulation and therapeutic resistance, etc., showing great value in cancer studies. [31,32] Cancer-derived sEVs are small, lipid bilayer membrane vesicles generated inside the cell in multivesicular bodies (MVBs), which release cancerderived sEVs into the extracellular microenvironment by fusion with the cell membrane (Fig. 1).…”

“…Cancer-derived sEVs have been reported to play different roles in PDAC, including cancer initiation, progression, metastasis, drug resistance, cancer diagnosis/ prognosis and treatment. [32,35,48] In this review, we will mainly focus on the most recent progress in the use of key molecules of cancer-derived sEVs as emerging biomarkers for PDAC diagnosis/prognosis and cancer-derived sEVs based therapeutic strategies for PDAC treatment, as well as discussing the current hurdles and perspectives for further clinical applications, with the aim of gaining new insights for researchers working on sEVs in cancer diagnosis/prognosis and treatment.…”