PMID- 32218180 OWN - NLM STAT- MEDLINE DCOM- 20210415 LR - 20210415 IS - 2218-273X (Electronic) IS - 2218-273X (Linking) VI - 10 IP - 4 DP - 2020 Mar 25 TI - Proteomic Analysis of Blood Exosomes from Healthy Females and Breast Cancer Patients Reveals an Association between Different Exosomal Bioactivity on Non-tumorigenic Epithelial Cell and Breast Cancer Cell Migration in Vitro. LID - 10.3390/biom10040495 [doi] LID - 495 AB - Exosomes are important intercellular communication vehicles, secreted into body fluids by multiple cell types, including tumor cells. They contribute to the metastatic progression of tumor cells through paracrine signalling. It has been recently discovered that blood circulating exosomes contain distinguishable fractions of free and cell-surface-associated vesicles. We evaluated the influence of protein cargoes from exosomes from plasma, and exosomes from the total blood of healthy females (HFs) and breast cancer patients (BCPs), on cell motility. We conducted a mass spectrometric analysis of exosomal contents isolated from samples using ultrafiltration and ultracentrifugation approaches and verified their nature using transmission electron microscopy, nanoparticle tracking analysis and flow cytometry. We observed that malignant neoplasm-associated proteins in exosomes from BCP total blood were detected more often than in plasma (66% vs. 59%). FunRich analysis to assess Gene Ontology (GO) enrichment revealed that proteins with catalytic activities, transporter functions and protein metabolism activities were increased in exosomes from BCP blood. Finally, GO analysis revealed that proteomic profiles of exosomes from HF total blood were enriched with proteins inhibiting cell migration and invasion, which explains the low stimulating activity of exosomes from HF total blood on SKBR-3 cancer cell migration velocity. This allows exosomes to act as intermediaries providing intercellular communications through horizontal transfer of RNA and functionally active proteins, potentially affecting the development of both primary neoplasms and distant metastases. FAU - Tutanov, Oleg AU - Tutanov O AD - Laboratory of Molecular Medicine, Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia. FAU - Orlova, Evgeniya AU - Orlova E AD - Laboratory of Carcinogenesis Mechanisms, "N.N. Blokhin Cancer Research Center" of the Ministry of Health of the Russian Federation, 115478 Moscow, Russia. FAU - Proskura, Ksenia AU - Proskura K AD - Laboratory of Molecular Medicine, Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia. AD - Department of Mammology, Novosibirsk Regional Clinical Oncological Dispensary, 630108 Novosibirsk, Russia. FAU - Grigor'eva, Alina AU - Grigor'eva A AD - Laboratory of Molecular Medicine, Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia. FAU - Yunusova, Natalia AU - Yunusova N AD - Laboratory of Tumor Biochemistry, Cancer Research Institute, capital TE, Cyrillicomsk National Research Medical Center, Russian Academy of Science, 634028 Tomsk, Russia. AD - Department of Biochemistry and Molecular Biology, Siberian State Medical University, 634050 Tomsk, Russia. FAU - Tsentalovich, Yuri AU - Tsentalovich Y AD - Laboratory of Proteomics and Metabolomics, International Tomography Center SB RAS, 630090 Novosibirsk, Russia. FAU - Alexandrova, Antonina AU - Alexandrova A AD - Laboratory of Carcinogenesis Mechanisms, "N.N. Blokhin Cancer Research Center" of the Ministry of Health of the Russian Federation, 115478 Moscow, Russia. FAU - Tamkovich, Svetlana AU - Tamkovich S AD - Laboratory of Molecular Medicine, Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia. AD - Department of Molecular Biology and Biotechnology, Novosibirsk State University, 630090 Novosibirsk, Russia. LA - eng GR - 18-415-540012/capital ER, Cyrillicsmall o, Cyrillicsmall es, Cyrillicsmall es, Cyrillicsmall i, Cyrillicsmall short i, Cyrillicsmall es, Cyrillicsmall ka, Cyrillicsmall i, Cyrillicsmall short i, Cyrillic capital EF, Cyrillicsmall o, Cyrillicsmall en, Cyrillicsmall de, Cyrillic capital EF, Cyrillicsmall u, Cyrillicsmall en, Cyrillicsmall de, Cyrillicsmall a, Cyrillicsmall em, Cyrillicsmall ie, Cyrillicsmall en, Cyrillicsmall te, Cyrillicsmall a, Cyrillicsmall el, Cyrillicsmall soft sign, Cyrillicsmall en, Cyrillicsmall yeru, Cyrillicsmall ha, Cyrillic capital I, Cyrillicsmall es, Cyrillicsmall es, Cyrillicsmall el, Cyrillicsmall ie, Cyrillicsmall de, Cyrillicsmall o, Cyrillicsmall ve, Cyrillicsmall a, Cyrillicsmall en, Cyrillicsmall i, Cyrillicsmall short i, Cyrillic (capital ER, Cyrilliccapital EF, Cyrilliccapital EF, Cyrilliccapital I, Cyrillic)/International PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200325 PL - Switzerland TA - Biomolecules JT - Biomolecules JID - 101596414 RN - 0 (Antigens, CD) RN - 0 (Membrane Proteins) RN - 0 (Proteins) RN - EC 3.4.- (Amyloid Precursor Protein Secretases) RN - EC 3.4.24.81 (ADAM10 Protein) RN - EC 3.4.24.81 (ADAM10 protein, human) SB - IM MH - ADAM10 Protein/blood MH - Adult MH - Aged MH - Amyloid Precursor Protein Secretases/blood MH - Antigens, CD/metabolism MH - Breast Neoplasms/blood/*pathology MH - Cell Line, Tumor MH - *Cell Movement MH - Cell-Free System MH - Epithelial Cells/metabolism/pathology MH - Exosomes/*metabolism/transplantation MH - Female MH - Humans MH - Membrane Proteins/blood MH - Middle Aged MH - Proteins/*analysis/metabolism MH - Proteomics/methods PMC - PMC7226042 OTO - NOTNLM OT - breast cancer OT - exosomes OT - mass-spectrometry OT - migration COIS- The authors declare no conflict of interest. EDAT- 2020/03/29 06:00 MHDA- 2021/04/16 06:00 PMCR- 2020/04/01 CRDT- 2020/03/29 06:00 PHST- 2020/02/26 00:00 [received] PHST- 2020/03/23 00:00 [revised] PHST- 2020/03/24 00:00 [accepted] PHST- 2020/03/29 06:00 [entrez] PHST- 2020/03/29 06:00 [pubmed] PHST- 2021/04/16 06:00 [medline] PHST- 2020/04/01 00:00 [pmc-release] AID - biom10040495 [pii] AID - biomolecules-10-00495 [pii] AID - 10.3390/biom10040495 [doi] PST - epublish SO - Biomolecules. 2020 Mar 25;10(4):495. doi: 10.3390/biom10040495.