J Cancer 2020; 11(1):213-228. doi:10.7150/jca.35821 This issue

Research Paper

Knockdown of serine/threonine-protein kinase 24 promotes tumorigenesis and myeloid-derived suppressor cell expansion in an orthotopic immunocompetent gastric cancer animal model

Hui-Ping Hsu1, Chih-Yang Wang2,3, Pei-Yin Hsieh2, Jung-Hua Fang4, Yi-Ling Chen5,6✉

1. Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
2. Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
3. Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan
4. Laboratory Animal Center, College of Medicine, National Cheng Kung University, Tainan, Taiwan
5. Department of Senior Citizen Service Management, Chia Nan University of Pharmacy and Science, Tainan, Taiwan
6. Senior Citizen Development Center, Chia Nan University of Pharmacy and Science, Tainan, Taiwan

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Citation:
Hsu HP, Wang CY, Hsieh PY, Fang JH, Chen YL. Knockdown of serine/threonine-protein kinase 24 promotes tumorigenesis and myeloid-derived suppressor cell expansion in an orthotopic immunocompetent gastric cancer animal model. J Cancer 2020; 11(1):213-228. doi:10.7150/jca.35821. Available from https://www.jcancer.org/v11p0213.htm

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Abstract

A higher incidence of gastric cancer has been found in East Asia compared to the incidence in other regions. Gastric cancer patients have a poor prognosis due to distant metastasis and advanced cancer stages. Tumor escape pathways include the expansion of the immunosuppressive myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment. We have successfully established an orthotopic immunocompetent gastric cancer model in C57BL/6 mice. The cell line is named M12 and was deposited at the Bioresource Collection and Research Center of Taiwan on Sep. 13, 2016 (Patent No. I604054). The orthotopic animal model of gastric cancer has similar biological characteristics as human gastric cancer. Serine/threonine-protein kinase 24 (STK24) is a member of the germinal center kinase (GCK)-III family. GCKs participate in cancer and immunological disorders. The effects of STK24 in gastric cancer are less well understood. CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 technology was used to induce a STK24 genetic knockout at the genomic DNA level in tumor cells. The knockdown of the STK24 gene increased the tumor growth in an orthotopic model of gastric cancer. The STK24 gene silencing in tumors induced the expansion of CD11b+Ly6C+ cells and F4/80+ macrophages in vivo. To our knowledge, we have developed the first orthotopic transplantable model of gastric cancer in syngeneic inbred mice. Our results further indicate that STK24 is important for immune regulation during the tumorigenesis of gastric cancer.

Keywords: gastric cancer, serine/threonine-protein kinase 24, myeloid-derived suppressor cells, germinal center kinase, tumorigenesis, orthotopic model of gastric cancer