Method for searching and screening for target of anti-cancer agent using non-human animal model having nog established cancer cell line transplanted therein

Abstract

An objective of the present invention is to provide non-human animal models of cancer pathology, which mimic the hierarchical organization, cancer progression process, or biological property of human cancer tissues, and uses thereof. To achieve the objective described above, first, the present inventors transplanted cells of NOG-established cancer lines into NOG mice and morphologically observed the resulting tissue organization. As a result, the non-human animal models were demonstrated to exhibit pathologies (the hierarchical organization, cancer progression process, or biological properties of the cancer cells) similar to that of human cancer. Specifically, the present inventors succeeded in preparing non-human animal models exhibiting pathologies more similar to a human cancer, and cell culture systems using NOG-established cancer cell lines where the in vitro cell morphology is more similar to that of human cancer.

1 . A non-human animal model, which is obtained by transplanting, into a non-human animal of the same or different species, an NOG-established cancer cell line established by transplanting a human tumor tissue into a severely-immunodeficient NOD/SCID/gamma(c)(null) (NOG) mouse wherein the non-human animal model mimics hierarchical organization or cancer progression process of a human cancer tissue. 
     
     
         2 . The non-human animal model of  claim 1 , which enables detection of a unique cancer stem cell having a characteristic for mimicking hierarchical organization and cancer progression process of a human cancer tissue, and testing of a biological property of the human cancer tissue. 
     
     
         3 . The non-human animal model of  claim 1 , which enables observation of the process leading to transition of a cancer cell into a tumor stroma-forming fibroblast through complete epithelial-mesenchymal transition (complete-EMT) during the process that mimics hierarchical organization of a human cancer tissue. 
     
     
         4 . A non-human animal model, which enables assessment of the cause of anti-cancer agent resistance by administering an anti-cancer agent into the non-human animal model of  claim 1 , and assessing, as an indicator, hierarchical organization, cancer progression process, or biological property of a cancer cell, or transition through complete epithelial-mesenchymal transition (complete-EMT). 
     
     
         5 . The non-human animal model of  claim 1 , wherein the human tumor tissue is derived from colon cancer, stomach cancer, breast cancer, lung cancer, or pancreatic cancer.