Establishment, molecular and biological characterization of HCB-514: a novel human cervical cancer cell line

Autor(es):Mostrar menos -

Rosa, Marcela Nunes ^[1] ; Evangelista, Adriane Feijo ^[1] ; Leal, Leticia Ferro ^[1] ; De Oliveira, Cristina Mendes ^[1] ; Oliveira Silva, Viviane Aline ^[1] ; Munari, Carla Carolina ^[1] ; Munari, Fernanda Franco ^[1] ; Matsushita, Graziela De Macedo ^[2] ; Dos Reis, Ricardo ^[3] ; Andrade, Carlos Eduardo ^[3] ; Souza, Cristiano de Padua ^[3] ; Reis, Rui Manuel ^{[4, 1, 5]}

Afiliação do(s) autor(es)

^[1] Barretos Canc Hosp, Mol Oncol Res Ctr, Barretos, SP - Brazil

^[2] Barretos Canc Hosp, Dept Pathol, Barretos, SP - Brazil

^[3] Barretos Canc Hosp, Dept Gynecol Oncol, Barretos, SP - Brazil

^[4] Univ Minho, Sch Hlth Sci, Life & Hlth Sci Res Inst ICVS, Braga - Portugal

^[5] 3Bs PT Govt Associate Lab, Braga - Portugal

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 9, FEB 13 2019.
• Citações Web of Science: 1

Resumo

Cervical cancer is the fourth most common cancer in women. Although cure rates are high for early stage disease, clinical outcomes for advanced, metastatic, or recurrent disease remain poor. To change this panorama, a deeper understanding of cervical cancer biology and novel study models are needed. Immortalized human cancer cell lines such as HeLa constitute crucial scientific tools, but there are few other cervical cancer cell lines available, limiting our understanding of a disease known for its molecular heterogeneity. This study aimed to establish novel cervical cancer cell lines derived from Brazilian patients. We successfully established one (HCB-514) out of 35 cervical tumors biopsied. We confirmed the phenotype of HCB-514 by verifying its' epithelial and tumor origin through cytokeratins, EpCAM and p16 staining. It was also HPV-16 positive. Whole-exome sequencing (WES) showed relevant somatic mutations in several genes including BRCA2, TGFBR1 and IRX2. A copy number variation (CNV) analysis by nanostring and WES revealed amplification of genes mainly related to kinases proteins involved in proliferation, migration and cell differentiation, such as EGFR, PIK3CA, and MAPK7. Overexpression of EGFR was confirmed by phospho RTK-array and validated by western blot analysis. Furthermore, the HCB-514 cell line was sensitive to cisplatin. In summary, this novel Brazilian cervical cancer cell line exhibits relevant key molecular features and constitutes a new biological model for pre-clinical studies. (AU)

• Processo FAPESP: 15/20077-3 - Detecção de DNA de HPV de alto risco e análises do status mutacional dos genes KRAS e PIK3CA e do painel de citocinas inflamatórias em pacientes com câncer de esôfago e megaesôfago chagásico com e sem câncer
• Beneficiário: Fernanda Franco Munari
• Modalidade de apoio: Bolsas no Brasil - Mestrado