Method for constructing in-situ primary gastric cancer animal model

Abstract

The invention discloses a preparation method of an in-situ primary gastric cancer tumor model, and belongs to the field of tumor animal models. The method comprises the following steps: culturing mouse gastric epithelial cells into organoids by using a specific culture medium, carrying out genetic modification on the organoids, and injecting the modified organoids back to the mouse stomach so as to develop the organoids into tumors. Compared with a transplanted tumor animal model, the method provided by the invention has a clear gene mutation background, and can effectively simulate the real process of occurrence and development of human gastric cancer. Compared with a genetic engineering tumor animal model, the gastric cancer mouse model with different gene mutation backgrounds can be efficiently constructed, the consumed time is short, the cost is low, and the tumor formation rate is high.

Description

technical field [0001] The invention belongs to the field of tumor animal models. Background technique [0002] Gastric cancer has become the tumor with the second incidence and the third death rate in my country. However, in the past two decades, there has been no breakthrough in the clinical treatment of gastric cancer. It is particularly urgent to gain an in-depth understanding of the mechanism of gastric cancer, find the key factors involved, and develop more effective treatments. Tumor animal models play a vital role in exploring the mechanism of tumor development and developing new drugs. The mouse model of gastric cancer provides a powerful tool for studying the mechanism of gastric cancer occurrence and metastasis, screening of antitumor drugs, and evaluation of immunotherapy. [0003] Currently, commonly used mouse models of gastric cancer mainly include xenograft models and spontaneous tumor models. The xenograft tumor model uses immunodeficient mice (such as a...

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Problems solved by technology

[0004] However, the current mouse gastric cancer model has many shortcomings, and it is insufficient to meet the needs of basic and preclinical research.

The transplanted rumen cancer model in mice has always been controversial, because the transplanted tumor is not a spontaneously formed tumor in the mouse body, and cannot reflect the real process of tumor formation in vivo; more importantly, the immune system of the body is very important in the process of tumor formation. Immunodeficient mice lack a complete immune system, and the use of transplanted rumen cancer models can no longer meet the needs of tumor immunotherapy research

The spontaneous tumorigenesis model based on genetically engineered mice has been recognized for its similarity to the tumorigenesis process in humans, but tumorigenesis is a process of cumulative changes in multiple genes, and traditional genetically engineered mice only introduce one or two gene changes at a time , if you want to obtain multiple gene mutant mice, you need multiple mating iterations; it takes a long time, if you want to obtain a large number of tumor mice of the same genotype at the same time, you need more parental mice, and the research cost increases

At the same time, because genetically engineered mice have germline mutations, they are prone to induce tumors in multiple systems and organs, which is also different from the actual occurrence of tumors; and due to individual differences in mice, the cycle of spontaneous tumor formation also varies greatly, making it difficult to achieve synchronization

More importantly, the technical threshold for the construction of genetically engineered mice is high, and the construction of new genotype mouse models takes a long period of time and costs high, and general research institutions cannot routinely carry out

For the chemically induced mouse gastric cancer model, the construction time of this type of model is relatively long, and the tumor formation has obvious individual differences. The high heterogeneity may cause the difficulty of later data processing. According to literature reports, the overall tumor formation is about 50%

Most importantly, this type of model lacks clear genetic manipulation and is not suitable for pathogenesis studies

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