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Association of extracellular vesicles derived from fibroblasts with the progression of Oral Squamous Cell Carcinoma

Grant number: 18/15728-3
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): August 01, 2019
Effective date (End): September 30, 2021
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Adriana Franco Paes Leme
Grantee:Jamile de Oliveira Sá
Host Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia e Inovação (Brasil). Campinas , SP, Brazil


The Cancer-Associated Fibroblast (CAFs) represent the main cellular components of the tumor microenvironment of many Carcinomas. In oral Squamous Cell Carcinoma (OSCC), the most common tumor of the oral cavity, CAF have been shown to promote tumor cell migration and invasion, proliferation, adhesion, immunosuppression, angiogenesis and worsen the patients' prognosis. Cancer-derived EV exert and play an important role in the signaling between the epithelium and stroma during the malignant transformation and tumoral progression. EVs are a heterogeneous group of nanometer-sized circulating particles composed of a lipid bilayer and loaded with transmembrane and cytosolic proteins as well as DNA and different types of RNA. Notably, the emerging evidence suggests that EV derived from tumor microenvironment may modulate recipient cells, contributing to the formation of a highly complex stroma able to modulate the invasive and metastatic potential of the cancer cells. To better understand the role of CAFs within the tumor stroma during the development of OSCC, this project aims to identify molecular signatures for of tumor progression through the proteomic study of fibroblasts-derived extracellular vesicles from primary fibroblasts from normal oral mucosa, oral potentially malignant disorders and OSCC. In addition, will be evaluated the effects of CAF-EV on OSCC cell invasion, proliferation, epithelial-mesenchymal transition of cell lines HMK, DOK, SCC-9 and HSC-3. It is expected (i) characterize the proteins associated with tumor progression; (ii) evaluate their correlation with the clinical characteristics of the patients and (iii) evaluate the functional role of the EVs derived from cancer-associated fibroblasts and the molecular mechanisms involved in the progression of oral OSCC. (AU)

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Scientific publications
(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)
SA, JAMILE DE OLIVEIRA; TRINO, LUCIANA DANIELE; OLIVEIRA, ANA KARINA; BUSSO LOPES, ARIANE FIDELIS; GRANATO, DANIELA CAMPOS; COSTA NORMANDO, ANA GABRIELA; SANTOS, ERISON SANTANA; NEVES, LEANDRO XAVIER; CARNIELLI, CAROLINA MORETTO; PAES LEME, ADRIANA FRANCO. Proteomic approaches to assist in diagnosis and prognosis of oral cancer. EXPERT REVIEW OF PROTEOMICS, v. 18, n. 4, p. 261-284, . (18/11958-4, 19/21815-9, 18/18496-6, 18/12194-8, 19/18751-9, 19/09692-9, 18/02180-0, 18/15535-0, 18/15728-3, 16/19337-3)
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)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
SÁ, Jamile de Oliveira. Potential markers in fibroblasts and extracellular vesicles of oral leukoplakia can antecipate malignant transformation to oral squamous cell carcinoma. 2021. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Faculdade de Odontologia de Piracicaba Piracicaba, SP.

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