Data documento
02/05/2024

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

Autor(es)
LAUS, Ana Carolina - GOMES, Izabela Natalia Faria - SILVA, Aline Larissa Virginio da - SILVA, Luciane Sussuchi da - MILAN, Mirella Baroni - TEIXEIRA, Silvia Aparecida - MARTINS, Ana Carolina Baptista Moreno - PEREIRA, Letícia do Nascimento Braga - CARVALHO, Carlos Eduardo Barbosa de - CROVADOR, Camila Souza - PAULA, Flávia Escremin de - NASCIMENTO, Flávia Caroline - FREITAS, Helder Teixeira de - VAZQUEZ, Vinicius de Lima - REIAS, Rui Manuel - OLIVEIRA, Renato José da Silva.

Palavras chave
Cutaneous squamous cell carcinoma - Molecular profile - Cell line establishment - In vivo model

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.

Citação
Laus AC, Gomes INF, da Silva ALV, da Silva LS, Milan MB, AparecidaTeixeira S, Martin ACBM, do Nascimento Braga Pereira L, de Carvalho CEB, Crovador CS, de Paula FE, Nascimento FC, de Freitas HT, de Lima Vazquez V, Reis RM, da Silva-Oliveira RJ. Establishment and molecular characterization of HCB-541, a novel and aggressive human cutaneous squamous cell carcinoma cell line. Hum Cell. 2024 Apr 3. doi: 10.1007/s13577-024-01054-1. Epub ahead of print. PMID: 38565739.

Data documento
19/03/2025

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

Autor(es)
Laus AC - Gomes INF - da Silva ALV - da Silva LS - Milan MB - AparecidaTeixeira S - Martin ACBM - do Nascimento Braga Pereira L - de Carvalho CEB - Crovador CS - de Paula FE - Nascimento FC - de Freitas HT - de Lima Vazquez V - Reis RM - da Silva-Oliveira RJ

Palavras chave
Cell line establishment; Cutaneous squamous cell carcinoma; In vivo model; Molecular profile.

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.

Citação
Laus AC, Gomes INF, da Silva ALV, da Silva LS, Milan MB, AparecidaTeixeira S, Martin ACBM, do Nascimento Braga Pereira L, de Carvalho CEB, Crovador CS, de Paula FE, Nascimento FC, de Freitas HT, de Lima Vazquez V, Reis RM, da Silva-Oliveira RJ. Hum Cell. 2024 Jul;37(4):1170-1183. doi: 10.1007/s13577-024-01054-1. Epub 2024 Apr 3. PMID: 38565739