Comprehensive model for simultaneous monitoring of primary tumor to metastatic cancer utilizing Prkdc and Il2rg double knockout mice

Sci Rep. 2024 Oct 9;14(1):23531. doi: 10.1038/s41598-024-75493-z.

Abstract

Liver cancer is the second leading cause of cancer-related deaths worldwide, motivating major scientific efforts to understand and treat this cancer type. Over 30% of patients with liver cancer progress to metastasis, which reduces the survival rate. Extensive studies on primary tumors have been conducted to improve the prognosis. However, there is a lack of appropriate and accessible models for studying the progression and metastasis of liver cancer. Moreover, conventional metastasis models do not reproduce metastasis as it occurs in patients. To address this lack of an appropriate model for the monitoring of cancer progression and evaluation of anticancer drugs, we established a spontaneous metastatic xenograft model using NSG mice subcutaneously transplanted with SK-Hep-1 cells. Compared to the conventional experimental metastasis model (intravenous transplantation), in which only lung metastasis was observed, the established spontaneous metastatic xenograft model was superior, as it showed both a primary tumor and metastatic patterns similar to those observed in human patients. Additionally, this model was successfully used to assess the antimetastatic efficacy of sorafenib. In conclusion, our results demonstrate that the established spontaneous metastatic xenograft model better reflects liver cancer metastasis and can be utilized to assess the efficacy of anticancer drugs for liver cancer.

Keywords: Liver neoplasms; Mice; Neoplastic processes; Sorafenib; Survival rate; Xenografts.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Cell Line, Tumor
  • Disease Models, Animal
  • Humans
  • Interleukin Receptor Common gamma Subunit* / deficiency
  • Interleukin Receptor Common gamma Subunit* / genetics
  • Liver Neoplasms* / drug therapy
  • Liver Neoplasms* / genetics
  • Liver Neoplasms* / secondary
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Lung Neoplasms / secondary
  • Mice
  • Mice, Inbred NOD
  • Mice, Knockout
  • Neoplasm Metastasis
  • Sorafenib / pharmacology
  • Sorafenib / therapeutic use
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Il2rg protein, mouse
  • Interleukin Receptor Common gamma Subunit
  • Sorafenib