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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: MOLECULAR & CELLULAR PROTEOMICS; v. 20, 2021.
• Citações Web of Science: 0

Resumo

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)

• Processo FAPESP: 15/19191-6 - Análise proteômica do fronte de invasão em carcinomas de células escamosas de cabeça e pescoço com metástase regional
• Beneficiário: Ariane Fidelis Busso Lopes
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 18/18496-6 - O papel do álcool na transformação de células orais mediada por vesículas extracelulares
• Beneficiário: Adriana Franco Paes Leme
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 10/19278-0 - Estudo da regulação de ADAMs em câncer oral
• Beneficiário: Adriana Franco Paes Leme
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 16/07846-0 - Análise peptidômica de vesículas extracelulares originadas de linhagens celulares, saliva e plasma de pacientes com carcinoma de células escamosas da cavidade oral
• Beneficiário: Adriana Franco Paes Leme
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 19/21815-9 - Análise de N-terminômica "multiplex" dos secretomas gerados pela MMP-2 e ADAM17 em culturas de cardiomiócitos utilizando a proteômica quantitativa com TMT-TAILS
• Beneficiário: Ariane Fidelis Busso Lopes
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado