Establishment and molecular characterization of HCB-541, a novel and aggressive human cutaneous squamous cell carcinoma cell line

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Laus, Ana Carolina ; Gomes, Izabela Natalia Faria ; da Silva, Aline Larissa Virginio ; da Silva, Luciane Sussuchi ; Milan, Mirella Baroni ; AparecidaTeixeira, Silvia ; Martin, Ana Carolina Baptista Moreno ; Pereira, Leticia do Nascimento Braga ; de Carvalho, Carlos Eduardo Barbosa ; Crovador, Camila Souza ; de Paula, Flavia Escremin ; Nascimento, Flavia Caroline ; de Freitas, Helder Teixeira ; Vazquez, Vinicius de Lima ; Reis, Rui Manuel ; da Silva-Oliveira, Renato Jose

• Tipo de documento: Artigo Científico
• Fonte: HUMAN CELL; v. 37, n. 4, p. 14-pg., 2024-04-03.

Resumo

Cutaneous squamous cell carcinoma (cSCC) is a common type of skin cancer that can result in significant morbidity, although it is usually well-managed and rarely metastasizes. However, the lack of commercially available cSCC cell lines hinders our understanding of this disease. This study aims to establish and characterize a new metastatic cSCC cell line derived from a Brazilian patient. A tumor biopsy was taken from a metastatic cSCC patient, immortalized, and named HCB-541 after several passages. The cytokeratin expression profile, karyotypic alterations, mutational analysis, mRNA and protein differential expression, tumorigenic capacity in xenograft models, and drug sensitivity were analyzed. The HCB-541 cell line showed a doubling time between 20 and 30 h and high tumorigenic capacity in the xenograft mouse model. The HCB-541 cell line showed hypodiploid and hypotetraploidy populations. We found pathogenic mutations in TP53 p.(Arg248Leu), HRAS (Gln61His) and TERT promoter (C228T) and high-level microsatellite instability (MSI-H) in both tumor and cell line. We observed 37 cancer-related genes differentially expressed when compared with HACAT control cells. The HCB-541 cells exhibited high phosphorylated levels of EGFR, AXL, Tie, FGFR, and ROR2, and high sensitivity to cisplatin, carboplatin, and EGFR inhibitors. Our study successfully established HCB-541, a new cSCC cell line that could be useful as a valuable biological model for understanding the biology and therapy of metastatic skin cancer. (AU)

• Processo FAPESP: 23/02032-9 - KRASgetaway: investigação pré-clínica para controle do oncogene KRAS
• Beneficiário: Renato José da Silva Oliveira
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 17/22305-9 - Estudo de biomarcadores de resposta ao cetuximabe e perspectivas do uso de combi-moléculas anti-EGFR em tumores sólidos
• Beneficiário: Izabela Natalia Faria Gomes
• Modalidade de apoio: Bolsas no Brasil - Doutorado