Kupffer cells suppress hepatocarcinogenesis and metastasis in tumor orthotopic implanted Kunming mice
1Department of Hepatobiliary surgery, Traditonal Chinese Medicine Hospital of Dianjiang, Chongqing, China
Abstract:
In this research, we used GdCl3 (gadolinium chloride) to restrain the function of Kupffer cells and assessed effects on hepatocarcinogenesis and metastasis in the Kunming mouse. A 0.25% GdCl3 solution (10 mg/kg b.w.) was infused via the vena caudalis of each mouse 1 week before inoculation of H22 cells and was continued once per three days. Then we observed the follow indexes 3 weeks after injection of H22 cells: tumor weight, histologic characteristics of tumor tissue by light microscopy, ultramicrostructure of Kupffer cells under the electron microscope, distribution and number of Kupffer cells by histochemical staining, and TNF-α and IFN-γ levels in blood-serum and liver tissue by ELISA and RT-PCR. MMP-2 protein expression was tested by immunohistochemistry. The GdCl3 pretreatment had no effect on the quantity of Kupffer cells, but clearly restrained their functions, with decrease of TNF-α and IFN-γ levels and elevation of MMP2. Tumor immunity functions were markedly suppressed and tumor growth was accelerated with appearance of metastasis. Furthermore, survival time of trial mice was shortened.
Insights
Gadolinium chloride (GdCl3) restrains Kupffer cell function, suppressing anti-tumor immunity. This leads to accelerated liver cancer growth, metastasis, and reduced survival in mice.
Area of Science:
- Hepatology
- Immunology
- Oncology
Background:
- Kupffer cells play a crucial role in liver immunity and cancer surveillance.
- Modulating Kupffer cell function is a potential strategy for cancer therapy.
Purpose of the Study:
- To investigate the effects of gadolinium chloride (GdCl3) on Kupffer cell function.
- To assess the impact of GdCl3-mediated Kupffer cell inhibition on hepatocarcinogenesis and metastasis.
Main Methods:
- GdCl3 was administered to Kunming mice before H22 hepatoma cell inoculation.
- Kupffer cell function, cytokine levels (TNF-α, IFN-γ), MMP-2 expression, tumor growth, metastasis, and survival were evaluated.
Main Results:
- GdCl3 inhibited Kupffer cell function without altering their quantity.
- Decreased TNF-α and IFN-γ levels and increased MMP-2 were observed.
- Tumor immunity was suppressed, leading to accelerated tumor growth, metastasis, and shortened survival.
Conclusions:
- GdCl3 effectively restrains Kupffer cell function, impairing anti-tumor immunity.
- Inhibiting Kupffer cells promotes hepatocarcinogenesis and metastasis, highlighting their critical role in liver cancer progression.
