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Peptidomic analysis of extracelular vesicles originated from cell lines, saliva and plasma from oral squamous cell carcinoma


The most common type of oral cancer is the squamous cell carcinoma (OSCC), the malign neoplasm originated from stratified squamous epithelium. The estimate number of cancer in Brazil for 2016 indicates about 600.000 new cases, which 15.490 would be new cases of cancer in the oral cavity, 11.140 in men and 4.350 in women (INCA, 2016). The most common prognostic factor is the clinical stage, based on TNM classification. However, this system is not perfect, mainly because tumor with similar morphology and stage can present different behavior associated with distinct biological characteristics. Besides that, another challenge is to correlate the histopathological information and the prognosis, which cannot reflect the biology of tumor. Therefore, there is a need to explore the mechanisms of disease, to improve the clinical decision for prognosis, to evaluate the risk of patients, to evaluate the recurrence as well as to guide to specific therapeutic approaches. The extracellular vesicles (EV) has emerged in the last years as mediators of intercellular signaling and as a new manner to promote cell-cell communication. Especially in cancer, EVs has been involved in the preparation of pre-metastatic site, because can act as messengers of different molecules, such as proteins, lipids, metabolites, RNA and DNA. Besides the characterization and functions of EVs that have been explored by our group in OSCC, one question remains unclear, which is the protein processing that dynamically occurs inside the EVs or the selection of peptides exported in the EVs. The bioactive peptides can carry conserved sequences that can regulate paracrine and autocrine targets. The identification and knowledge of the role of these peptides in EVs can reveal new molecules involved in the tumor progression. The nanotracking combined with discovery-based proteomics are robust techniques to quantify EVs and identify the peptides. Therefore, this project aims to characterize peptides of EVs extracted from (1) cell lines originated or not from metastasis site, SCC-9 LN1 and SCC-9, (2) saliva and (3) plasma from patients with clinical staging N0 with T3 and T4, and N+ with T1 and T2. We expected to characterize the bioactive peptides in EVs, (ii) to correlate this information with the clinical-pathological information and (iii) to explore their function in biological events associated with oral cancer. (AU)

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Scientific publications (8)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
RIVERA, CESAR; ZANDONADI, FLAVIA SILVA; SANCHEZ-ROMERO, CELESTE; SOARES, CIRO DANTAS; GRANATO, DANIELA CAMPOS; ALEJANDRO GONZALEZ-ARRIAGADA, WILFREDO; PAES LEME, ADRIANA FRANCO. Agrin has a pathological role in the progression of oral cancer. BRITISH JOURNAL OF CANCER, v. 118, n. 12, p. 1628-1638, . (16/07846-0, 10/19278-0, 09/54067-3)
RIVERA, CESAR; OLIVEIRA, ANA KARINA; PEREIRA COSTA, RUTE ALVES; DE ROSSI, TATIANE; PAES LEME, ADRIANA FRANCO. Prognostic biomarkers in oral squamous cell carcinoma: A systematic review. Oral Oncology, v. 72, p. 38-47, . (15/12431-1, 16/07846-0, 14/06485-9)
PALMIER, NATALIA RANGEL; PAES LEME, ADRIANA FRANCO; DE ROSSI, TATIANE; TELLES, GUILHERME PIMENTEL; MORAIS-FARIA, KARINA; KOWALSKI, LUIZ PAULO; MARTA, GUSTAVO NADER; BRANDAO, THAIS BIANCA; ARANY, PRAVEEN R.; MIGLIORATI, CESAR AUGUSTO; et al. Salivary alpha-1-antitrypsin and macrophage migration inhibitory factor may be potential prognostic biomarkers for oncologic treatment-induced severe oral mucositis. SUPPORTIVE CARE IN CANCER, v. 29, n. 6, p. 2939-2946, . (18/04657-8, 15/12431-1, 12/06138-1, 13/18402-8, 16/22862-2, 16/07846-0, 18/02233-6)
BUSSO-LOPES, ARIANE FIDELIS; CARNIELLI, CAROLINA MORETTO; WINCK, FLAVIA VISCHI; DE SA PATRONI, FABIO MALTA; OLIVEIRA, ANA KARINA; GRANATO, DANIELA CAMPOS; PEREIRA E COSTA, RUTE ALVES; DOMINGUES, ROMENIA RAMOS; PAULETTI, BIANCA ALVES; RIANO-PACHON, DIEGO MAURICIO; et al. A Reductionist Approach Using Primary and Metastatic Cell-Derived Extracellular Vesicles Reveals Hub Proteins Associated with Oral Cancer Prognosis. MOLECULAR & CELLULAR PROTEOMICS, v. 20, . (15/19191-6, 18/18496-6, 10/19278-0, 16/07846-0, 19/21815-9)
NEVES, LEANDRO XAVIER; GRANATO, DANIELA C.; BUSSO-LOPES, ARIANE FIDELIS; CARNIELLI, CAROLINA M.; DE SA PATRONI, FABIO M.; DE ROSSI, TATIANE; OLIVEIRA, ANA KARINA; RIBEIRO, ANA CAROLINA P.; BRANDAO, THAIS BIANCA; RODRIGUES, ANDRE NIMTZ; et al. Peptidomics-Driven Strategy Reveals Peptides and Predicted Proteases Associated With Oral Cancer Prognosis. MOLECULAR & CELLULAR PROTEOMICS, v. 20, . (09/54067-3, 18/11958-4, 18/18496-6, 10/19278-0, 16/07846-0)
E COSTA, RUTE A. P.; GRANATO, DANIELA C.; TRINO, LUCIANA D.; YOKOO, SAMI; CARNIELLI, CAROLINA M.; KAWAHARA, REBECA; DOMINGUES, ROMENIA R.; PAULETTI, BIANCA ALVES; NEVES, LEANDRO XAVIER; SANTANA, ALINE G.; et al. ADAM17 cytoplasmic domain modulates Thioredoxin-1 conformation and activity. REDOX BIOLOGY, v. 37, . (16/01528-7, 18/12194-8, 19/18751-9, 18/18496-6, 09/54067-3, 18/15535-0, 14/23888-0, 16/07846-0, 16/24664-3, 14/06485-9, 10/19278-0)
GRANATO, DANIELA C.; NEVES, LEANDRO X.; TRINO, LUCIANA D.; CARNIELLI, CAROLINA M.; LOPES, ARIANE F. B.; YOKOO, SAMI; PAULETTI, BIANCA A.; DOMINGUES, ROMENIA R.; SA, JAMILE O.; PERSINOTI, GABRIELLA; et al. Meta-omics analysis indicates the saliva microbiome and its proteins associated with the prognosis of oral cancer patients. BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS, v. 1869, n. 8, . (18/18496-6, 18/02180-0, 16/07846-0, 19/18751-9, 19/21815-9, 09/54067-3, 18/11958-4, 15/50590-4, 18/12194-8, 18/15728-3, 14/06485-9, 18/15535-0, 10/19278-0)
CARNIELLI, CAROLINA MORETTO; SOARES MACEDO, CAROLINA CARNEIRO; DE ROSSI, TATIANE; GRANATO, DANIELA CAMPOS; RIVERA, CESAR; DOMINGUES, ROMENIA RAMOS; PAULETTI, BIANCA ALVES; YOKOO, SAMI; HEBERLE, HENRY; BUSSO-LOPES, ARIANE FIDELIS; et al. Combining discovery and targeted proteomics reveals a prognostic signature in oral cancer. NATURE COMMUNICATIONS, v. 9, . (13/16483-0, 09/53998-3, 16/07846-0, 10/19278-0, 09/54067-3)

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