Perera Chamini J, Falasca Marco, Chari Suresh T, Greenfield Jerry R, Xu Zhihong, Pirola Romano C, Wilson Jeremy S, Apte Minoti V
Pancreatic Research Group, South Western Sydney Clinical School, Faculty of Medicine and Health, UNSW Sydney, Sydney 2052, Australia.
Ingham Institute for Applied Medical Research, Sydney 2170, Australia.
Cancers (Basel). 2021 Oct 18;13(20):5224. doi: 10.3390/cancers13205224.
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 β 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 β 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 β 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.
胰腺导管腺癌（PDAC）是一种严重的疾病，其特征为症状不明确且诊断延迟。约30%的PDAC患者报告有新发糖尿病史，通常在癌症诊断前3年内被诊断出来。因此，新发糖尿病，也称为胰腺癌相关糖尿病（PCRD），可能是PDAC的先兆。糖尿病是由进行性β细胞丢失/功能障碍和胰岛素抵抗驱动的，这两个关键特征在PCRD中也存在。实验研究表明，PDAC细胞衍生的外泌体携带对β细胞功能和胰岛素敏感性有害的因子。然而，基质细胞，特别是胰腺星状细胞（PSC）在PCRD发病机制中的作用尚不清楚。PSC存在于最早的肿瘤病变周围和胰岛周围。鉴于PSC与癌细胞密切相互作用以推动癌症进展，癌细胞和PSC的外泌体货物可能在调节β细胞功能和外周胰岛素抵抗中起作用。鉴定这些介质可能有助于阐明PCRD的机制并有助于早期检测PDAC。本文讨论了PSC在PCRD发病机制中的新作用这一概念。
