Tumor-Educated Platelet Extracellular Vesicles: Proteomic Profiling and Crosstalk with Colorectal Cancer Cells.
Simple Summary: The most life-threatening events in colorectal cancer (CRC) are metastasis and thrombosis. Platelets can play a role in these outcomes via the release of medium-sized extracellular vesicles (mEVs). Thus, we aimed to study the EVs released from activated platelets of CRC patients and...
| Publicado en: | Cancers Vol. 15; no. 2; pp. 350 - 372 |
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| Autores principales: | , , , , , , , , , , , , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
MDPI
Jan2023
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=161438722&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 161438722 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 20726694 B74B jtl: Cancers issn: 20726694 maglogo: N pubinfo: dt: Jan2023 vid: 15 iid: 2 pid: 97109 pub: MDPI artinfo: ui: 161438722 161438722 161438722 10.3390/cancers15020350 161438722 ppf: 350 ppct: 22 formats: tig: atl: Tumor-Educated Platelet Extracellular Vesicles: Proteomic Profiling and Crosstalk with Colorectal Cancer Cells. aug: au: Contursi, Annalisa Fullone, Rosa Szklanna-Koszalinska, Paulina Marcone, Simone Lanuti, Paola Taus, Francesco Meneguzzi, Alessandra Turri, Giulia Dovizio, Melania Bruno, Annalisa Pedrazzani, Corrado Tacconelli, Stefania Marchisio, Marco Ballerini, Patrizia Minuz, Pietro Maguire, Patricia Patrignani, Paola affil: Center for Advanced Studies and Technology (CAST), 66100 Chieti, Italy sug: subj: Colorectal Neoplasms Physiopathology Blood Platelets Metabolism Extracellular Vesicles Metabolism Proteomics Neoplasm Metastasis Thrombosis Human Funding Source Epithelial-Mesenchymal Transition Cell Line, Tumor Metabolism Cox-2 Inhibitors Gene Expression Proteins Metabolism Extracellular Vesicles Physiopathology ab: Simple Summary: The most life-threatening events in colorectal cancer (CRC) are metastasis and thrombosis. Platelets can play a role in these outcomes via the release of medium-sized extracellular vesicles (mEVs). Thus, we aimed to study the EVs released from activated platelets of CRC patients and healthy controls (HS) for their size composition, protein content, and the capacity to influence the expression of genes involved in malignancy and the synthesis of a prothrombotic lipid mediator such as thromboxane (TX)A2. Our findings show that the protein content of thrombin-stimulated mEVs is modulated in CRC. Its evaluation may represent a noninvasive tool to discriminate patients from healthy subjects. Moreover, our findings show that characterizing the regulation of the expression of promalignant genes and prothrombotic phenotypes in cancer cells by the crosstalk with platelet mEVs could provide prognostic information on cancer patients, which could help in developing an appropriate anticancer strategy. Background: Platelet–cancer cell interactions modulate tumor metastasis and thrombosis in cancer. Platelet-derived extracellular vesicles (EVs) can contribute to these outcomes. Methods: We characterized the medium-sized EVs (mEVs) released by thrombin-stimulated platelets of colorectal cancer (CRC) patients and healthy subjects (HS) on the capacity to induce epithelial-mesenchymal transition (EMT)-related genes and cyclooxygenase (COX)-2(PTGS2), and thromboxane (TX)B2 production in cocultures with four colorectal cancer cell lines. Platelet-derived mEVs were assessed for their size distribution and proteomics signature. Results: The mEV population released from thrombin-activated platelets of CRC patients had a different size distribution vs. HS. Platelet-derived mEVs from CRC patients, but not from HS, upregulated EMT marker genes, such as TWIST1 and VIM, and downregulated CDH1. PTGS2 was also upregulated. In cocultures of platelet-derived mEVs with cancer cells, TXB2 generation was enhanced. The proteomics profile of mEVs released from activated platelets of CRC patients revealed that 119 proteins were downregulated and 89 upregulated vs. HS. Conclusions: We show that mEVs released from thrombin-activated platelets of CRC patients have distinct features (size distribution and proteomics cargo) vs. HS and promote prometastatic and prothrombotic phenotypes in cancer cells. The analysis of platelet-derived mEVs from CRC patients could provide valuable information for developing an appropriate treatment plan. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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