Analysis of ovarian cancer cell secretome during epithelial to mesenchymal transition reveals a protein signature associated with advanced stages of ovarian tumors

Autor(es)

Lanfredi, Guilherme P. ^[1] ; Thome, Carolina H. ^{[2, 3, 4]} ; Ferreira, Germano A. ^{[2, 3, 4]} ; Silvestrini, Virginia C. ^[1] ; Masson, Ana P. ^[1] ; Vargas, Alessandra P. ^[1] ; Grassi, Mariana L. ^[1] ; Poersch, Aline ^[1] ; Candido dos Reis, Francisco J. ^[2] ; Faca, Vitor M. ^{[3, 1, 4]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Biochem & Immunol, Av Bandeirantes 3900, BR-14048900 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Gynecol & Obstet, Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Ctr Cell Based Therapy, Ribeirao Preto Med Sch, Ribeirao Preto - Brazil

^[4] Univ Sao Paulo, Reg Blood Ctr Ribeirao Preto, Ribeirao Preto Med Sch, Ribeirao Preto - Brazil

• Tipo de documento: Artigo Científico
• Fonte: BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS; v. 1869, n. 6 JUN 2021.
• Citações Web of Science: 0

Resumo

Ovarian cancer (OvCA) is the most lethal neoplasia among gynecologic malignancies and faces high rates of new cases particularly in South America. In special, the High Grade Serous Ovarian Carcinoma (HGSC) presents very poor prognosis with deaths caused mainly by metastasis. Among several mechanisms involved in metastasis, the Epithelial to Mesenchymal Transition (EMT) molecular reprogramming represents a model for latest stages of cancer progression. EMT promotes important cellular changes in cellular adhesion and cell-cell communication, which particularly depends on the paracrine signaling from neighbor cells. Considering the importance of cellular communication during EMT and metastasis, here we analyzed the changes in the secretome of the ovarian cancer cell line Caov-3 induced to EMT by Epidermal Growth Factor (EGF). Using a combination of GEL-LC-MS/MS and stable isotopic metabolic labelling (SILAC), we identified up-regulated candidates during EMT as a starting point to identify relevant proteins for HGSC. Based on public databases, our candidate proteins were validated and prioritized for further analysis. Importantly, several of the protein candidates were associated with cellular vesicles, which are important to the cell-cell communication and metastasis. Furthermore, the association of candidate proteins with gene expression data uncovered a subset of proteins correlated with the mesenchymal subtype of ovarian cancer. Based on this relevant molecular signature for aggressive ovarian cancer, supported by protein and gene expression data, we developed a targeted proteomic method to evaluate individual OvCA clinical samples. The quantitative information obtained for 33 peptides, representative of 18 proteins, was able to segregate HGSC from other tumor types. Our study highlighted the richness of the secretome and EMT to reveal relevant proteins for HGSC, which could be used in further studies and larger patient cohorts as a potential stratification signature for ovarian cancer tumor that could guide clinical conduct for patient treatment. (AU)

• Processo FAPESP: 13/07675-3 - Estudo da via de sinalização pi3k/akt em leucemia mielóide aguda utilizando o monitoramento seletivo de ions (srm).
• Beneficiário: Carolina Hassibe Thomé
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 16/03809-3 - Estudo proteômico dirigido da localização e translocação subcelular de proteínas na transição epitélio-mesenquimal
• Beneficiário: Vitor Marcel Faça
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/08135-2 - CTC - Centro de Terapia Celular
• Beneficiário: Dimas Tadeu Covas
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs