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Oncogenic and non‐malignant pancreatic exosome cargo reveal distinct expression of oncogenic and prognostic factors involved in tumor invasion and metastasis
journal contributionposted on 17.03.2021, 01:17 by Aikaterini Emmanouilidi, Dino Paladin, David Greening, Marco Falasca
© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Exosomes are small extracellular membrane vesicles important in intercellular communication, with their oncogenic cargo attributed to tumor progression and pre-metastatic niche formation. To gain an insight into key differences in oncogenic composition of exosomes, human non-malignant epithelial and pancreatic cancer cell models and purified and characterized resultant exosome populations are utilized. Proteomic analysis reveals the selective enrichment of known exosome markers and signaling proteins in comparison to parental cells. Importantly, valuable insights into oncogenic exosomes (362 unique proteins in comparison to non-malignant exosomes) of key metastatic regulatory factors and signaling molecules fundamental to pancreatic cancer progression (KRAS, CD44, EGFR) are provided. It is reported that oncogenic exosomes contain factors known to regulate the pre-metastatic niche (S100A4, F3, ITGβ5, ANXA1), clinically-relevant proteins which correlate with poor prognosis (CLDN1, MUC1) as well as protein networks involved in various cancer hallmarks including proliferation (CLU, CAV1), invasion (PODXL, ITGA3), metastasis (LAMP1, ST14) and immune surveillance escape (B2M). The presence of these factors in oncogenic exosomes offers an understanding of select differences in exosome composition during tumorigenesis, potential components as prognostic and diagnostic biomarkers in pancreatic cancer, and highlights the role of exosomes in mediating crosstalk between tumor and stromal cells.
This work was supported by Avner Pancreatic Cancer Foundation (grants to M.F.) and AB Analitica. A.E. is supported by the Curtin International Postgraduate Research Scholarship (CIPRS)/AB Analitica Scholarship. D.W.G. is supported by National Health and Medical Research Council of Australia project Grants #1141946 and #1139489, La Trobe Institute for Molecular Science Fellowship, La Trobe University Leadership Research Focus grant, and La Trobe University Start-up Fund. A.E. and M.F. also acknowledge the infrastructure and staff support provided by CHIRI, School of Pharmacy & Biomedical Sciences and Faculty of Health Sciences, Curtin University. Part of this research was undertaken using the Zeiss Neon 40EsB Cross-beam FESEM instrumentation (ARC LE0775553) at the John de Laeter Centre, Curtin University.
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Science & TechnologyLife Sciences & BiomedicineBiochemical Research MethodsBiochemistry & Molecular Biologyexosomesmetastasispancreatic cancerpre-metastatic nicheproteomicsSPLICED TISSUE FACTORBREAST-CANCERNICHE FORMATIONPROTEOMIC ANALYSISPROTEINSCELLSIDENTIFICATIONMICROVESICLESBIOMARKERSCD44PancreasCell Line, TumorHumansPancreatic NeoplasmsBlotting, WesternCell CommunicationMass SpectrometryExosomesTumor Microenvironment