Journal
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
Volume -, Issue 175, Pages -Publisher
JOURNAL OF VISUALIZED EXPERIMENTS
DOI: 10.3791/62630
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Funding
- National Health and Medical Research Council [APP1156391, APP1081852, APP1140236, APP1099283]
- Cancer Council SA Beat Cancer Project
- State Government of South Australia through the Department of Health [MCF0418]
- Ministry of Education, Culture, Sports, Science and Technology of Japan [20H03467]
- AMED-CREST (Japan Agency for Medical Research and Development, Core Research for Evolutional Science and Technology) [19gm0810007h0104, 19gm1210008s0101]
- Project for Cancer Research and Therapeutic Evolution (P-CREATE) from AMED [19cm0106332h0002]
- Japan Society for the Promotion of Science Overseas Challenge Program for Young Researchers
- Takeda Science Foundation Fellowship
- Greaton International Ph.D. Scholarship
- Lions Medical Research Foundation Scholarship
- Grants-in-Aid for Scientific Research [20H03467] Funding Source: KAKEN
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Liver metastasis of colorectal cancer is a major cause of cancer-related death. Cancer-associated fibroblasts play a crucial role in metastatic CRC progression and poor patient prognosis. A new mouse model using CRC organoids injection into the portal vein has been developed to study the interaction between metastatic cancer cells and CAFs, providing a useful platform for assessing novel therapeutic strategies.
Hepatic metastasis of colorectal cancer (CRC) is a leading cause of cancer-related death. Cancer-associated fibroblasts (CAFs), a major component of the tumor microenvironment, play a crucial role in metastatic CRC progression and predict poor patient prognosis. However, there is a lack of satisfactory mouse models to study the crosstalk between metastatic cancer cells and CAFs. Here, we present a method to investigate how liver metastasis progression is regulated by the metastatic niche and possibly could be restrained by stroma-directed therapy. Portal vein injection of CRC organoids generated a desmoplastic reaction, which faithfully recapitulated the fibroblast-rich histology of human CRC liver metastases. This model was tissue-specific with a higher tumor burden in the liver when compared to an intrasplenic injection model, simplifying mouse survival analyses. By injecting luciferaseexpressing tumor organoids, tumor growth kinetics could be monitored by in vivo imaging. Moreover, this preclinical model provides a useful platform to assess the efficacy of therapeutics targeting the tumor mesenchyme. We describe methods to examine whether adeno-associated virus-mediated delivery of a tumor-inhibiting stromal gene to hepatocytes could remodel the tumor microenvironment and improve mouse survival. This approach enables the development and assessment of novel therapeutic strategies to inhibit hepatic metastasis of CRC.
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