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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

A Reductionist Approach Using Primary and Metastatic Cell-Derived Extracellular Vesicles Reveals Hub Proteins Associated with Oral Cancer Prognosis

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Busso-Lopes, Ariane Fidelis [1] ; Carnielli, Carolina Moretto [1] ; Winck, Flavia Vischi [2] ; de Sa Patroni, Fabio Malta [1] ; Oliveira, Ana Karina [1] ; Granato, Daniela Campos [1] ; Pereira E Costa, Rute Alves [1] ; Domingues, Romenia Ramos [1] ; Pauletti, Bianca Alves [1] ; Riano-Pachon, Diego Mauricio [2] ; Aricetti, Juliana [3] ; Caldana, Camila [4] ; Graner, Edgard [5] ; Della Coletta, Ricardo [5] ; Dryden, Kelly [6] ; Fox, Jay William [7] ; Paes Leme, Adriana Franco [1]
Total Authors: 17
[1] Ctr Nacl Pesquisa Energia & Mat CNPEM, Lab Nacl Biociencias LNBio, Campinas, SP - Brazil
[2] Univ Sao Paulo, Inst Quim, Dept Bioquim, Lab Biol Sistemas Regulatorios, Sao Paulo, SP - Brazil
[3] Ctr Nacl Pesquisa Energia & Mat CNPEM, Lab Nacl Biorrenovaveis LNBR, Campinas, SP - Brazil
[4] Max Planck Inst Mol Plant Physiol, Potsdam - Germany
[5] Univ Estadual Campinas, Fac Odontol Piracicaba, Dept Diagnost Oral, Piracicaba, SP - Brazil
[6] Univ Virginia, Mol Electron Microscopy Core, Charlottesville, VA - USA
[7] Univ Virginia, Dept Microbiol Immunol & Canc Biol, Charlottesville, VA - USA
Total Affiliations: 7
Document type: Journal article
Web of Science Citations: 0

Oral squamous cell carcinoma (OSCC) has high mortality rates that are largely associated with lymph node metastasis. However, the molecular mechanisms that drive OSCC metastasis are unknown. Extracellular vesicles (EVs) are membrane-bound particles that play a role in intercellular communication and impact cancer development and progression. Thus, profiling EVs would be of great significance to decipher their role in OSCC metastasis. For that purpose, we used a reductionist approach to map the proteomic, miRNA, metabolomic, and lipidomic profiles of EVs derived from human primary tumor (SCC-9) cells and matched lymph node metastatic (LN1) cells. Distinct omics profiles were associated with the metastatic phenotype, including 670 proteins, 217 miRNAs, 26 metabolites, and 63 lipids differentially abundant between LN1 cell- and SCC-9 cellderived EVs. A multi-omics integration identified 11 `hub proteins' significantly decreased at the metastatic site compared with primary tumor-derived EVs. We confirmed the validity of these findings with analysis of data from multiple public databases and found that low abundance of seven `hub proteins' in EVs from metastatic lymph nodes (ALDH7A1, CAD, CANT1, GOT1, MTHFD1, PYGB, and SARS) is correlated with reduced survival and tumor aggressiveness in patients with cancer. In summary, this multi-omics approach identified proteins transported by EVs that are associated with metastasis and which may potentially serve as prognostic markers in OSCC. (AU)

FAPESP's process: 15/19191-6 - Proteomic analysis of the invasive front in head and neck squamous cell carcinomas with regional metastasis
Grantee:Ariane Fidelis Busso Lopes
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 18/18496-6 - The role of alcohol treated-extracellular vesicles in oral cells transformation
Grantee:Adriana Franco Paes Leme
Support type: Research Projects - Thematic Grants
FAPESP's process: 10/19278-0 - Study of regulation of ADAMs in oral cancer
Grantee:Adriana Franco Paes Leme
Support type: Research Grants - Young Investigators Grants
FAPESP's process: 16/07846-0 - Peptidomic analysis of extracelular vesicles originated from cell lines, saliva and plasma from oral squamous cell carcinoma
Grantee:Adriana Franco Paes Leme
Support type: Regular Research Grants
FAPESP's process: 19/21815-9 - Multiplex N-terminomics analysis of cardiomyocyte secretome based on MMP-2 and ADAM17 activity using TMT-TAILS quantitative proteomics
Grantee:Ariane Fidelis Busso Lopes
Support type: Scholarships in Brazil - Post-Doctorate