Heterozygous loss of Dip2B enhances tumor growth and metastasis by altering immune microenvironment

Salah Adlat; Farooq Hayel; Yang Chen; Rajiv Kumar Sah; Zin Mar Oo; Mahmoud Al-Azab; May Zun Zaw Myint; Noor Bahadar; Fatoumata Binta Bah; Nasser Mi; Mohammed Safi; Xuechao Feng; Ping Zhu; Yaowu Zheng

doi:10.1016/j.intimp.2022.108559

Heterozygous loss of Dip2B enhances tumor growth and metastasis by altering immune microenvironment

Int Immunopharmacol. 2022 Apr:105:108559. doi: 10.1016/j.intimp.2022.108559. Epub 2022 Jan 25.

Authors

Salah Adlat¹, Farooq Hayel², Yang Chen³, Rajiv Kumar Sah⁴, Zin Mar Oo², Mahmoud Al-Azab⁵, May Zun Zaw Myint², Noor Bahadar², Fatoumata Binta Bah², Nasser Mi⁶, Mohammed Safi⁷, Xuechao Feng⁸, Ping Zhu⁹, Yaowu Zheng¹⁰

Affiliations

¹ Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510100, China; Transgenic Research Center, School of Life Sciences, Northeast Normal University, Changchun, Jilin 130024, China.
² Transgenic Research Center, School of Life Sciences, Northeast Normal University, Changchun, Jilin 130024, China.
³ Transgenic Research Center, School of Life Sciences, Northeast Normal University, Changchun, Jilin 130024, China; School of Life Sciences, Xuzhou Medical University, Jiangsu, Xuzhou 221004, China.
⁴ Transgenic Research Center, School of Life Sciences, Northeast Normal University, Changchun, Jilin 130024, China; School of Medicine, Southern University of Science and Technology, Shenzhen 518005, Guangdong, China.
⁵ Department of Immunology, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Centre, Guangzhou Medical University, Guangzhou 510623, China.
⁶ Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510100, China.
⁷ Department of Oncology, First Affiliated Hospital of Dalian Medical University, Dalian, China.
⁸ Transgenic Research Center, School of Life Sciences, Northeast Normal University, Changchun, Jilin 130024, China. Electronic address: fengxc997@nenu.edu.cn.
⁹ Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510100, China. Electronic address: tanganqier@163.com.
¹⁰ Transgenic Research Center, School of Life Sciences, Northeast Normal University, Changchun, Jilin 130024, China; Cardiovascular Research Institute, University of California, San Francisco, CA 94158, United States. Electronic address: zhengyw442@nenu.edu.cn.

PMID: 35091337
DOI: 10.1016/j.intimp.2022.108559

Abstract

Cancer is caused by abnormal cell growth and metastasis to other tissues. Development of cancers is complex and underlining mechanisms are mostly unknown. Disco-interacting protein 2 homolog B (DIP2B) is a member of Dip2. There have been reports suggesting that Dip2B may participate in tumor growth and development. However, direct link between DIP2B and cancer development is missing. In this study, Dip2b^tm1a/+ heterozygous knockout mouse model was used to investigate tumor growth and metastasis. Results show that one allele knockout of Dip2B significantly promoted tumor growth and metastasis, decreased tumor cell apoptosis and reduced immune cell infiltration in tumors, most likely by altering immune system that includes reduction of macrophage and cytotoxic T-cells infiltration into tumor microenvironment.

Keywords: B16F10; Dip2B; Metastasis; RNA seq; Tumor.

MeSH terms

Animals
Cell Line, Tumor
Cell Proliferation / genetics
Macrophages
Mice
Mice, Knockout
Neoplasm Metastasis
Neoplasms* / genetics
Neoplasms* / immunology
Nerve Tissue Proteins* / genetics
Tumor Microenvironment* / genetics

Substances

Dip2b protein, mouse
Nerve Tissue Proteins