Fatty change of the liver microenvironment influences the metastatic potential of colorectal cancer
Autor: | Satoshi Masaki, Yoshimi Hashimoto, Shoma Kunisho, Yasuhiko Kitadai, Akiko Kimoto |
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Rok vydání: | 2020 |
Předmět: |
Stromal cell
Colorectal cancer colorectal cancer Diet High-Fat Pathology and Forensic Medicine Metastasis Mice chemistry.chemical_compound Liver disease Cell Line Tumor Tumor Microenvironment medicine metastasis Animals Humans Molecular Biology organ microenvironment Mice Inbred BALB C Methionine business.industry Macrophages Liver Neoplasms Fatty liver Original Articles Cell Biology medicine.disease Immunohistochemistry Choline Deficiency Fatty Liver Disease Models Animal Liver chemistry Cancer cell Cancer research Original Article Female Steatosis Colorectal Neoplasms business |
Zdroj: | International Journal of Experimental Pathology |
ISSN: | 1365-2613 0959-9673 |
DOI: | 10.1111/iep.12371 |
Popis: | Summary Fatty liver is the most common cause of liver disease, and its prevalence has been increasing globally. Colorectal cancer (CRC) accounts for approximately 10% of all cancers and metastasizes most commonly to the liver. Paget's ‘Seed and Soil’ theory of metastasis proposed that the secondary growth of cancer cells is dependent on the distal organ microenvironment. This implies that the risk of metastasis may change due to changes in the microenvironment of target organs. However, the association between steatosis, fatty change in the liver microenvironment, and liver metastasis has not been clarified. Here, we induced fatty liver conditions in BALB/c mice using a choline‐deficient high‐fat diet with 0.1% methionine (CDAHFD) and then injected the CT26 cells to produce experimental metastasis. The number of metastatic tumours was significantly increased in mice with severe fatty liver as compared to control mice. The average size of metastatic tumours was smaller in mice with moderate fatty liver than in control mice. The stromal components, including cancer‐associated fibroblasts, tumour‐associated macrophages and tumour‐infiltrating lymphocytes, were also examined. Metastatic tumours in fatty liver showed invasive growth patterns without a fibrotic capsule. Compared to control groups, the polarization of macrophages and subtypes of tumour‐infiltrating lymphocytes differed depending on the extent of fatty liver progression. These results indicated that fatty changes in the liver influenced liver metastasis of CRC. Although moderate fatty changes suppress the growth of metastatic tumours in the liver, a severe fatty microenvironment may promote invasion and metastasis through alteration of the tumour microenvironment (TME). |
Databáze: | OpenAIRE |
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