<p>Hepatic sarcomatoid carcinoma (HSC) is a rare and highly aggressive liver malignancy with an extremely poor prognosis. The lack of well-validated cellular models has severely limited mechanistic and translational research on this disease. In this study, we established and comprehensively characterized a novel HSC cell line, designated PUMC-LICA3. This cell line was derived from surgically resected tumor tissue of a 58-year-old male patient and has been continuously cultured for more than 40 passages, with a population doubling time of 51.77&#xa0;h and an epithelial-like morphology. Long-read sequencing identified HBV DNA integration at chromosome 17p11.2 without detectable covalently closed circular DNA (cccDNA) or viral antigen expression, indicating a non-replicative viral status. PUMC-LICA3 exhibited 100% tumorigenicity in NOD/SCID mice. Xenograft tumors displayed immunohistochemical features consistent with sarcomatoid carcinoma, characterized by the co-expression of epithelial markers (CK and CK19) and the mesenchymal marker vimentin. E-cadherin expression was patchy, with partial loss in subsets of tumor cells, whereas N-cadherin was diffusely expressed. Notably, PUMC-LICA3 exhibited a high epithelial–mesenchymal transition (EMT) score and, among 22 hepatocellular carcinoma (HCC), clustered most closely with JHH-6 and SNU-387. Drug sensitivity assays showed that the cell line was sensitive to cisplatin, doxorubicin and sorafenib, but resistant to 5‑fluorouracil. Whole-exome sequencing (WES) analysis revealed that the cell line largely preserved the genetic characteristics of its parental tumor throughout long-term culture. In conclusion, the newly established PUMC-LICA3 cell line represents a reliable and valuable experimental model for investigating the biological characteristics and therapeutic strategies of hepatic sarcomatoid carcinoma.</p>

错误:搜索内容不能为空,请输入英文关键词
错误:关键词超出字数限制,请精简
高级检索

Establishment and characterization of a novel HBV-integrated hepatic sarcomatoid carcinoma cell line

  • Jiayin Dai,
  • Fang Cao,
  • Zhenli Yang,
  • Kun Dong,
  • Xiaozheng Huang,
  • Xiaocui Bian,
  • Yuqin Liu

摘要

Hepatic sarcomatoid carcinoma (HSC) is a rare and highly aggressive liver malignancy with an extremely poor prognosis. The lack of well-validated cellular models has severely limited mechanistic and translational research on this disease. In this study, we established and comprehensively characterized a novel HSC cell line, designated PUMC-LICA3. This cell line was derived from surgically resected tumor tissue of a 58-year-old male patient and has been continuously cultured for more than 40 passages, with a population doubling time of 51.77 h and an epithelial-like morphology. Long-read sequencing identified HBV DNA integration at chromosome 17p11.2 without detectable covalently closed circular DNA (cccDNA) or viral antigen expression, indicating a non-replicative viral status. PUMC-LICA3 exhibited 100% tumorigenicity in NOD/SCID mice. Xenograft tumors displayed immunohistochemical features consistent with sarcomatoid carcinoma, characterized by the co-expression of epithelial markers (CK and CK19) and the mesenchymal marker vimentin. E-cadherin expression was patchy, with partial loss in subsets of tumor cells, whereas N-cadherin was diffusely expressed. Notably, PUMC-LICA3 exhibited a high epithelial–mesenchymal transition (EMT) score and, among 22 hepatocellular carcinoma (HCC), clustered most closely with JHH-6 and SNU-387. Drug sensitivity assays showed that the cell line was sensitive to cisplatin, doxorubicin and sorafenib, but resistant to 5‑fluorouracil. Whole-exome sequencing (WES) analysis revealed that the cell line largely preserved the genetic characteristics of its parental tumor throughout long-term culture. In conclusion, the newly established PUMC-LICA3 cell line represents a reliable and valuable experimental model for investigating the biological characteristics and therapeutic strategies of hepatic sarcomatoid carcinoma.