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Role of Pancreatic Stellate Cell-Derived Exosomes in Pancreatic Cancer-Related Diabetes: A Novel Hypothesis


Pancreatic ductal adenocarcinoma (PDAC) is a devastating condition characterised by vague symptomatology and delayed diagnosis. About 30% of PDAC patients report a history of new onset diabetes, usually diagnosed within 3 years prior to the diagnosis of cancer. Thus, new onset diabetes, which is also known as pancreatic cancer-related diabetes (PCRD), could be a harbinger of PDAC. Diabetes is driven by progressive beta cell loss/dysfunction and insulin resistance, two key features that are also found in PCRD. Experimental studies suggest that PDAC cell-derived exosomes carry factors that are detrimental to beta cell function and insulin sensitivity. However, the role of stromal cells, particularly pancreatic stellate cells (PSCs), in the pathogenesis of PCRD is not known. PSCs are present around the earliest neoplastic lesions and around islets. Given that PSCs interact closely with cancer cells to drive cancer progression, it is possible that exosomal cargo from both cancer cells and PSCs plays a role in modulating beta cell function and peripheral insulin resistance. Identification of such mediators may help elucidate the mechanisms of PCRD and aid early detection of PDAC. This paper discusses the concept of a novel role of PSCs in the pathogenesis of PCRD.

Type Journal
ISBN 2072-6694 (Print) 2072-6694 (Linking)
Authors Perera, C. J.; Falasca, M.; Chari, S. T.; Greenfield, J. R.; Xu, Z.; Pirola, R. C.; Wilson, J. S.; Apte, M. V.
Responsible Garvan Author Prof Jerry Greenfield
Publisher Name Cancers
Published Date 2021-10-31
Published Volume 13
Published Issue 20
Published Pages 5224
Status Published in-print
DOI 10.3390/cancers13205224
URL link to publisher's version