The potential roles of exosomes in pancreatic cancer initiation and metastasis

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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.

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Most cited references 128

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Selective enrichment of tetraspan proteins on the internal vesicles of multivesicular endosomes and on exosomes secreted by human B-lymphocytes.

J Escola, M Kleijmeer, W Stoorvogel … (1998)

Association of major histocompatibility complex (MHC) class II molecules with peptides occurs in a series of endocytic vacuoles, termed MHC class II-enriched compartments (MIICs). Morphological criteria have defined several types of MIICs, including multivesicular MIICs, which are composed of 50-60-nm vesicles surrounded by a limiting membrane. Multivesicular MIICs can fuse with the plasma membrane, thereby releasing their internal vesicles into the extracellular space. The externalized vesicles, termed exosomes, carry MHC class II and can stimulate T-cells in vitro. In this study, we show that exosomes are enriched in the co-stimulatory molecule CD86 and in several tetraspan proteins, including CD37, CD53, CD63, CD81, and CD82. Interestingly, subcellular localization of these molecules revealed that they were concentrated on the internal membranes of multivesicular MIICs. In contrast to the tetraspans, other membrane proteins of MIICs, such as HLA-DM, Lamp-1, and Lamp-2, were mainly localized to the limiting membrane and were hardly detectable on the internal membranes of MIICs nor on exosomes. Because internal vesicles of multivesicular MIICs are thought to originate from inward budding of the limiting membrane, the differential distribution of membrane proteins on the internal and limiting membranes of MIICs has to be driven by active protein sorting.

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Recent progress in pancreatic cancer.

Christopher L. Wolfgang, Joseph M. Herman, Daniel Laheru … (2013)

Pancreatic cancer is currently one of the deadliest of the solid malignancies. However, surgery to resect neoplasms of the pancreas is safer and less invasive than ever, novel drug combinations have been shown to improve survival, advances in radiation therapy have resulted in less toxicity, and enormous strides have been made in the understanding of the fundamental genetics of pancreatic cancer. These advances provide hope but they also increase the complexity of caring for patients. It is clear that multidisciplinary care that provides comprehensive and coordinated evaluation and treatment is the most effective way to manage patients with pancreatic cancer. Copyright © 2013 American Cancer Society, Inc.

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Role of oncogenic KRAS in the diagnosis, prognosis and treatment of pancreatic cancer

Louis Buscail, Barbara Bournet, Pierre Cordelier (2020)

Pancreatic ductal adenocarcinoma (PDAC) is predicted to be the second most common cause of death within the next 10 years. The prognosis for this disease is poor despite diagnostic progress and new chemotherapeutic regimens. The oncogenic KRAS mutation is the major event in pancreatic cancer; it confers permanent activation of the KRAS protein, which acts as a molecular switch to activate various intracellular signalling pathways and transcription factors inducing cell proliferation, migration, transformation and survival. Several laboratory methods have been developed to detect KRAS mutations in biological samples, including digital droplet PCR (which displays high sensitivity). Clinical studies have revealed that a KRAS mutation assay in fine-needle aspiration material combined with cytopathology increases the sensitivity, accuracy and negative predictive value of cytopathology for a positive diagnosis of pancreatic cancer. In addition, the presence of KRAS mutations in serum and plasma (liquid biopsies) correlates with a worse prognosis. The presence of mutated KRAS can also have therapeutic implications, whether at the gene level per se, during its post-translational maturation, interaction with nucleotides and after activation of the various oncogenic signals. Further pharmacokinetic and toxicological studies on new molecules are required, especially small synthetic molecules, before they can be used in the therapeutic arsenal for pancreatic ductal adenocarcinoma.

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Author and article information

Contributors

Xiangxuan Zhao:

ORCID: http://orcid.org/0000-0003-1209-9995

xiangxuanzhao@163.com

Journal

Journal ID (nlm-ta): Mol Cancer

Journal ID (iso-abbrev): Mol. Cancer

Title: Molecular Cancer

Publisher: BioMed Central (London )

ISSN (Electronic): 1476-4598

Publication date (Electronic): 2 September 2020

Publication date PMC-release: 2 September 2020

Publication date Collection: 2020

Volume: 19

Electronic Location Identifier: 135

Affiliations

GRID grid.412467.2, ISNI 0000 0004 1806 3501, Department of Radiology, , Shengjing Hospital of China Medical University, ; 36 Sanhao Street, Heping District, Shenyang, 110004 Liaoning China

Author information

Xiangxuan Zhao http://orcid.org/0000-0003-1209-9995

Article

Publisher ID: 1255

DOI: 10.1186/s12943-020-01255-w

PMC ID: 7466807

PubMed ID: 32878635

SO-VID: d4a031d4-26dd-4449-96ef-e68809a8bc38

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 6 July 2020

Date accepted : 25 August 2020

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;

Award ID: 31371425

Award Recipient : Xiangxuan Zhao

Funded by: FundRef http://dx.doi.org/10.13039/501100005047, Natural Science Foundation of Liaoning Province;

Award ID: 20180551061

Award ID: 20180551174

Award Recipient : Ying Ren Xiangxuan Zhao

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ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: exosome,pancreatic cancer,tumorigenesis,metastasis,tumor biomarker

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ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: exosome, pancreatic cancer, tumorigenesis, metastasis, tumor biomarker

The potential roles of exosomes in pancreatic cancer initiation and metastasis

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Abstract

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Karger: Oncology

Most cited references 128

Selective enrichment of tetraspan proteins on the internal vesicles of multivesicular endosomes and on exosomes secreted by human B-lymphocytes.

Recent progress in pancreatic cancer.

Role of oncogenic KRAS in the diagnosis, prognosis and treatment of pancreatic cancer

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