The potential roles of exosomes in pancreatic cancer initiation and metastasis
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The potential roles of exosomes in pancreatic cancer initiation and metastasis Wei Sun, Ying Ren, Zaiming Lu and Xiangxuan Zhao*
Abstract Pancreatic cancer (PaCa) is an insidious and highly metastatic malignancy, with a 5-year survival rate of less than 5%. So far, the pathogenesis and progression mechanisms of PaCa have been poorly characterized. Exosomes correspond to a class of extracellular nanovesicles, produced by a broad range of human somatic and cancerous cells. These particular nanovesicles are mainly composed by proteins, genetic substances and lipids, which mediate signal transduction and material transport. A large number of studies have indicated that exosomes may play decisive roles in the occurrence and metastatic progression of PaCa. This article summarizes the specific functions of exosomes and their underlying molecular mechanisms in mediating the initiation and metastatic capability of PaCa. Keywords: Exosome, Pancreatic cancer, Tumorigenesis, Metastasis, Tumor biomarker
Background Pancreatic cancer (PaCa) ranks among the most common and devastating digestive tract cancers worldwide. Besides early surgical resection, no effective regime against this aggressive malignancy has been discovered so far [1]. The 5-year overall survival rate of PaCa is considered less than 5% and the survival period of advanced PaCa is only 3–6 months [2]. Remarkably, the carcinogenesis of PaCa remains poorly characterized. The majority of PaCa cases (over 85%) are attributed to pancreatic ductal adenocarcinoma (PDAC) [3]. Some studies have shown that acinar-to-ductal metaplasia (ADM), induced by pancreatic injury, pancreatitis, or genetic toxicity, is one of the most typical events observed during PaCa development. ADM can further evolve into a variety of pancreatic intraepithelial neoplasias (PanINs), which are, to some extent, still reversible. Under the influence of many factors, PanINs eventually progress into PDAC [4]. ADM can be recovered after the elimination of oncogenic genetic insults or sustained * Correspondence: [email protected] Department of Radiology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Heping District, Shenyang 110004, Liaoning, China
environmental stress [5]. It has been shown that matrix metalloproteinase-7 (MMP-7) [6], NAD (+) - dependent protein deacetylase sirtuin-1 (SIRT1) [7], and polycomb compressor complex 1 (PRC1) [8] are involved in the regulation of ADM development. In addition, atypical flat duct lesions (AFDL) have often been considered as precancerous conditions of PaCa [9]. Recent studies have also indicated that mutations on KRAS [10], m (6) A demethylase gene ALKBH5 [11], PDL-1 (CD274), and various non-coding RNAs [12] may play key roles in modulating the occurrence and development of PaCa. Still, despite many reports describing a plethora of signal pathways involved in PaCa initiation and progression, the underlying mechanisms that orchestrate the development of this malignancy are poorly known or still under debate. Exosomes
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