Panoply™ Human CTSC Over-expressing Stable Cell Line

Radiotherapy is an important treatment for advanced hepatocellular carcinoma (HCC), but limited understanding of the mechanisms of HCC radioresistance hinders its further clinical application. Here, researchers elucidate the crucial role of cathepsin C (CTSC) in regulating HCC radioresistance. Results showed that CTSC expression in HCC tissues was significantly higher than in adjacent non-tumor tissues. Correlation analysis indicated that high CTSC expression was positively correlated with various aggressive clinicopathological features, including increased tumor number, larger tumor volume, loss of tumor capsule, microvascular invasion, and later TNM stage. Survival analysis further revealed that CTSC overexpression was associated with shortened overall survival (OS) and progression-free survival (PFS) in HCC patients. In vitro experiments showed that CTSC overexpression improved the clonogenic survival rate of Huh7 cells after ionizing radiation (IR) and reduced the apoptosis rate. In subcutaneous and orthotopic liver tumor models, upregulated CTSC expression significantly reduced radiotherapy sensitivity. Clinically, CTSC overexpression is significantly associated with poor response to radiotherapy. Mechanistically, CTSCs promote the infiltration of myeloid-derived suppressor cells (MDSCs) by upregulating CXCL1 expression, while reducing the infiltration of CD8+ T cells.

Hepatocellular carcinoma (HCC) often occurs against a background of persistent liver inflammation and immune system dysregulation. Therefore, researchers hypothesized that CTSCs might accelerate HCC metastasis by altering the immune microenvironment. To test this hypothesis, researchers successfully constructed a CTSC-overexpressing Hepa1-6 cell line. Using a C57BL/6 mouse model of intrahepatic orthotopic tumor transplantation, they further investigated the role of CTSCs in HCC metastasis. Bioluminescence imaging showed a significantly enhanced signal intensity in the CTSC-overexpressing Hepa1-6 cell group (Figure 1A, B). Hematoxylin-eosin (HE) staining confirmed a higher incidence of lung metastasis and a greater number of lung nodules in the CTSC-overexpressing Hepa1-6 cell group (Figure 1D-F). Furthermore, CTSC overexpression shortened the overall survival of C57BL/6 mice (Figure 1C). In summary, these results indicate that CTSC overexpression plays a crucial role in promoting HCC metastasis.

Figure 1. CTSC overexpression promotes HCC metastasis. (Xu J, et al., 2026)