A method for constructing a liver cancer lung pre-metastasis niche mouse model associated with hardness

By constructing and applying tumor-free mouse models, we have solved the problems of stiffness-related animal experiments, especially for constructing tumor-free models and for studying stiffness-related animal models. We have also solved the construction method of stiffness-related liver cancer lung pre-metastatic niche mouse models, and solved the technical problems and difficulties. In particular, we have solved the experimental research on stiffness-related liver cancer lung pre-metastatic niches by constructing and applying tumor-free mouse models.

CN118633568BActive Publication Date: 2026-06-23ZHONGSHAN HOSPITAL FUDAN UNIV
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
ZHONGSHAN HOSPITAL FUDAN UNIV
Filing Date
2024-06-17
Publication Date
2026-06-23

AI Technical Summary

Technical Problem

The existing technology lacks an ideal animal model that can fully simulate the pre-metastatic niche of liver cancer in the lungs, especially a tumor-free mouse model, making it difficult to accurately assess the regulatory mechanism of matrix stiffness on the formation of distal pre-metastatic niches in liver cancer.

Method used

A method combining in vitro conditioned culture supernatant acquisition and in vivo injection induction was employed. Conditioned culture supernatant of mouse hepatocellular carcinoma cells growing on low and high hardness substrates was extracted in vitro to simulate soluble factors of primary hepatocellular carcinoma tumors in normal and high hardness backgrounds. These factors were then injected into mice via tail vein once a day until day 26. The recruitment of BMDCs in fresh lung tissue was detected to define the time point of lung pre-metastatic niche formation, supplemented by the detection of pre-metastatic niche marker characteristics at the induction endpoint.

Benefits of technology

A characteristic model capable of accurately assessing the formation of pre-metastatic niches in the lungs of hepatocellular carcinoma was constructed, including tumor-free mouse models of BMDC recruitment, matrix remodeling, inflammation, immunosuppression, angiogenesis, vascular permeability, and inflammation. The model can accurately simulate tumor-free mouse models with high and low lung tissue matrix remodeling, immunosuppression, angiogenesis, vascular permeability, and inflammation. The model can accurately reflect the characteristics of the model, solving the technical problem of stiffness-related animal models and achieving technical solutions to the technical problem.

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Abstract

The application discloses a kind of hardness correlation liver cancer lung premetastatic niche mouse model construction method, it includes the following steps: (1) in vitro enrichment respectively on the low hardness substrate of hardness 6kPa and the high hardness substrate of hardness 16kPa, the condition culture supernatant of mouse liver cancer cell Hepa1-6 that is cultured and grows, respectively named mL-CM and mH-CM;(2) mL-CM and mH-CM are respectively injected into two groups of mice using tail vein injection mode, every 1 day injection 1 time, until the 26th day, during continuous monitoring the recruitment of BMDCs in fresh lung tissue, while with the induction endpoint, i.e. 26th day premetastatic niche mark feature detection includes lung tissue matrix remodeling, immunosuppression, angiogenesis, vascular permeability and inflammation etc..The method has the advantages of short modeling cycle, easy operation, controllable induction condition, can comprehensively and accurately evaluate the common characteristics of liver cancer lung premetastatic niche formation etc..
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