The potential roles of exosomes in pancreatic cancer initiation and metastasis

Sun, Wei; Ren, Ying; Lu, Zaiming; Zhao, Xiangxuan

doi:10.1186/s12943-020-01255-w

Cited by 62 publications

(59 citation statements)

References 168 publications

(204 reference statements)

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“…The activation of various signaling pathways in target cells may be modulated by EVs, thus playing key roles in the pathogenesis and progression of several pancreatic precancerous conditions [19,20]. Indeed, these EVs are implicated in the transformation of various precancerous lesions into PC and in the progression of PC toward more invasive and metastasizing forms through the activation of mechanisms of angiogenesis, cell migration, epithelial-mesenchymal transition (EMT), and apoptotic resistance [21]. EVs may also serve as cytokine/immune-suppressive mediator shuttles in this setting.…”

Section: Introductionmentioning

confidence: 99%

Extracellular Vesicles and Pancreatic Cancer: Insights on the Roles of miRNA, lncRNA, and Protein Cargos in Cancer Progression

Romanò

Picca

Eusebi

et al. 2021

Cells

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Pancreatic cancer (PC) is among the most devastating digestive tract cancers worldwide. This cancer is characterized by poor diagnostic detection, lack of therapy, and difficulty in predicting tumorigenesis progression. Although mutations of key oncogenes and oncosuppressor involved in tumor growth and in immunosurveillance escape are known, the underlying mechanisms that orchestrate PC initiation and progression are poorly understood or still under debate. In recent years, the attention of many researchers has been concentrated on the role of extracellular vesicles and of a particular subset of extracellular vesicles, known as exosomes. Literature data report that these nanovesicles are able to deliver their cargos to recipient cells playing key roles in the pathogenesis and progression of many pancreatic precancerous conditions. In this review, we have summarized and discussed principal cargos of extracellular vesicles characterized in PC, such as miRNAs, lncRNAs, and several proteins, to offer a systematic overview of their function in PC progression. The study of extracellular vesicles is allowing to understand that investigation of their secretion and analysis of their content might represent a new and potential diagnostic and prognostic tools for PC.

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Section: Introductionmentioning

confidence: 99%

Extracellular Vesicles and Pancreatic Cancer: Insights on the Roles of miRNA, lncRNA, and Protein Cargos in Cancer Progression

Romanò

Picca

Eusebi

et al. 2021

Cells

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“…Cancer cell invasion of adjacent tissues and metastasis to distant sites are complex [ 56 ], multiscale processes. Invasion and metastasis contribute to high recurrence risk, poor prognosis, and low survival [ 57 , 58 ]. Cancer metabolism contributes to cancer cell viability and growth [ 59 ].…”

Section: Decreased Mpc1 Expression Promotes Tumour Progressionmentioning

confidence: 99%

Mitochondrial pyruvate carrier 1: a novel prognostic biomarker that predicts favourable patient survival in cancer

Xue

Bao

et al. 2021

Cancer Cell Int

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Mitochondrial pyruvate carrier 1 (MPC1) is a key metabolic protein that regulates the transport of pyruvate into the mitochondrial inner membrane. MPC1 deficiency may cause metabolic reprogramming. However, whether and how MPC1 controls mitochondrial oxidative capacity in cancer are still relatively unknown. MPC1 deficiency was recently found to be strongly associated with various diseases and cancer hallmarks. We utilized online databases and uncovered that MPC1 expression is lower in many cancer tissues than in adjacent normal tissues. In addition, MPC1 expression was found to be substantially altered in five cancer types: breast-invasive carcinoma (BRCA), kidney renal clear cell carcinoma (KIRC), lung adenocarcinoma (LUAD), pancreatic adenocarcinoma (PAAD), and prostate adenocarcinoma (PRAD). However, in KIRC, LUAD, PAAD, and PRAD, high MPC1 expression is closely associated with favourable prognosis. Low MPC1 expression in BRCA is significantly associated with shorter overall survival time. MPC1 expression shows strong positive and negative correlations with immune cell infiltration in thymoma (THYM) and thyroid carcinoma (THCA). Furthermore, we have comprehensively summarized the current literature regarding the metabolic reprogramming effects of MPC1 in various cancers. As shown in the literature, MPC1 expression is significantly decreased in cancer tissue and associated with poor prognosis. We discuss the potential metabolism-altering effects of MPC1 in cancer, including decreased pyruvate transport ability; impaired pyruvate-driven oxidative phosphorylation (OXPHOS); and increased lactate production, glucose consumption, and glycolytic capacity, and the underlying mechanisms. These activities facilitate tumour progression, migration, and invasion. MPC1 is a novel cancer biomarker and potentially powerful therapeutic target for cancer diagnosis and treatment. Further studies aimed at slowing cancer progression are in progress.

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“…Among these, exosomal RNAs have been intensively studied due to their essential roles in regulating all aspects of tumor metabolism and function [57]. In PaCa, cancer cells can be influenced by exosomal RNAs secreted from neighboring cancer cells or other cells, such as pancreatic stellate cells (PSCs), tumor-associated macrophages (TAMs), and cancerassociated fibroblasts (CAFs) [58][59][60]. Exosomal RNA delivery ultimately modulates the various features of PaCa, and many scholars have interpreted the role of exosomal RNAs in PaCa development and progression (Table 2).…”

Section: Exosomal Rnas Play Pivotal Roles In Paca Development and Progression (Fig 2)mentioning

confidence: 99%

The significance of exosomal RNAs in the development, diagnosis, and treatment of pancreatic cancer

Zhao

Yang

et al. 2021

Cancer Cell Int

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Exosomes are single-membrane, secreted organelles with a diameter of 30–200 nm, containing diverse bioactive constituents, including DNAs, RNAs, proteins, and lipids, with prominent molecular heterogeneity. Extensive studies indicate that exosomal RNAs (e.g., microRNAs, long non-coding RNAs, and circular RNAs) can interact with many types of cancers, associated with several hallmark features like tumor growth, metastasis, and resistance to therapy. Pancreatic cancer (PaCa) is among the most lethal cancers worldwide, emerging as the seventh foremost cause of cancer-related death in both sexes. Hence, revealing the specific pathogenesis and improving the clinical diagnosis and treatment process are urgently required. As the study of exosomes has become an active area of research, the functional connections between exosomes and PaCa have been deeply investigated. Among these, exosomal RNAs seem to play a significant role in the development, diagnosis, and treatment of PaCa. Exosomal RNAs delivery ultimately modulates the various features of PaCa, and many scholars have interpreted how exosomal RNAs contribute to the proliferation, angiogenesis, migration, invasion, metastasis, immune escape, and drug resistance in PaCa. Besides, recent studies emphasize that exosomal RNAs may serve as diagnostic and prognostic biomarkers or therapeutic targets for PaCa. In this review, we will introduce these recent insights focusing on the discoveries of the relationship between exosomal RNAs and PaCa, and the potentially diagnostic and therapeutic applications of exosomes in PaCa.

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The potential roles of exosomes in pancreatic cancer initiation and metastasis

Cited by 62 publications

References 168 publications

Extracellular Vesicles and Pancreatic Cancer: Insights on the Roles of miRNA, lncRNA, and Protein Cargos in Cancer Progression

Extracellular Vesicles and Pancreatic Cancer: Insights on the Roles of miRNA, lncRNA, and Protein Cargos in Cancer Progression

Mitochondrial pyruvate carrier 1: a novel prognostic biomarker that predicts favourable patient survival in cancer

The significance of exosomal RNAs in the development, diagnosis, and treatment of pancreatic cancer

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