PMID- 36639644 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230116 IS - 2049-3002 (Print) IS - 2049-3002 (Electronic) IS - 2049-3002 (Linking) VI - 11 IP - 1 DP - 2023 Jan 13 TI - Arginase-1 inhibition reduces migration ability and metastatic colonization of colon cancer cells. PG - 1 LID - 10.1186/s40170-022-00301-z [doi] LID - 1 AB - BACKGROUND: Arginase-1 (ARG1), a urea cycle-related enzyme, catalyzes the hydrolysis of arginine to urea and ornithine, which regulates the proliferation, differentiation, and function of various cells. However, it is unclear whether ARG1 controls the progression and malignant alterations of colon cancer. METHODS: We established metastatic colonization mouse model and ARG1 overexpressing murine colon cancer CT26 cells to investigate whether activation of ARG1 was related to malignancy of colon cancer cells in vivo. Living cell numbers and migration ability of CT26 cells were evaluated in the presence of ARG inhibitor in vitro. RESULTS: Inhibition of arginase activity significantly suppressed the proliferation and migration ability of CT26 murine colon cancer cells in vitro. Overexpression of ARG1 in CT26 cells reduced intracellular L-arginine levels, enhanced cell migration, and promoted epithelial-mesenchymal transition. Metastatic colonization of CT26 cells in lung and liver tissues was significantly augmented by ARG1 overexpression in vivo. ARG1 gene expression was higher in the tumor tissues of liver metastasis than those of primary tumor, and arginase inhibition suppressed the migration ability of HCT116 human colon cancer cells. CONCLUSION: Activation of ARG1 is related to the migration ability and metastatic colonization of colon cancer cells, and blockade of this process may be a novel strategy for controlling cancer malignancy. CI - (c) 2022. The Author(s). FAU - Wang, Xiangdong AU - Wang X AD - Division of Functional Immunology, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo, 060-0815, Japan. FAU - Xiang, Huihui AU - Xiang H AD - Division of Functional Immunology, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo, 060-0815, Japan. AD - Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, Yokohama, 241-8515, Japan. FAU - Toyoshima, Yujiro AU - Toyoshima Y AD - Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, 060-8638, Japan. FAU - Shen, Weidong AU - Shen W AD - Division of Functional Immunology, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo, 060-0815, Japan. FAU - Shichi, Shunsuke AU - Shichi S AD - Division of Functional Immunology, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo, 060-0815, Japan. AD - Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, 060-8638, Japan. FAU - Nakamoto, Hiroki AU - Nakamoto H AD - Division of Functional Immunology, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo, 060-0815, Japan. AD - Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, 060-8638, Japan. FAU - Kimura, Saori AU - Kimura S AD - Division of Functional Immunology, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo, 060-0815, Japan. AD - Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, 060-8638, Japan. FAU - Sugiyama, Ko AU - Sugiyama K AD - Division of Functional Immunology, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo, 060-0815, Japan. AD - Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, 060-8638, Japan. FAU - Homma, Shigenori AU - Homma S AD - Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, 060-8638, Japan. FAU - Miyagi, Yohei AU - Miyagi Y AD - Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, Yokohama, 241-8515, Japan. FAU - Taketomi, Akinobu AU - Taketomi A AD - Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, 060-8638, Japan. FAU - Kitamura, Hidemitsu AU - Kitamura H AD - Division of Functional Immunology, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo, 060-0815, Japan. kitamura@igm.hokudai.ac.jp. LA - eng PT - Journal Article DEP - 20230113 PL - England TA - Cancer Metab JT - Cancer & metabolism JID - 101607582 PMC - PMC9838026 OTO - NOTNLM OT - Arginase 1 OT - Arginine OT - Colorectal cancer OT - Malignancy OT - Metastatic colonization COIS- The authors declare that they have no competing interests. EDAT- 2023/01/14 06:00 MHDA- 2023/01/14 06:01 PMCR- 2023/01/13 CRDT- 2023/01/13 23:30 PHST- 2022/05/20 00:00 [received] PHST- 2022/12/14 00:00 [accepted] PHST- 2023/01/13 23:30 [entrez] PHST- 2023/01/14 06:00 [pubmed] PHST- 2023/01/14 06:01 [medline] PHST- 2023/01/13 00:00 [pmc-release] AID - 10.1186/s40170-022-00301-z [pii] AID - 301 [pii] AID - 10.1186/s40170-022-00301-z [doi] PST - epublish SO - Cancer Metab. 2023 Jan 13;11(1):1. doi: 10.1186/s40170-022-00301-z.