Methionine enkephalin inhibited cervical cancer migration as well as invasion and activated CD11b+ NCR1+ NKs of tumor microenvironment

Na Qu; Yiming Meng; Jingbo Zhai; Noreen Griffin; Yuanye Shan; Yuhua Gao; Fengping Shan

doi:10.1016/j.intimp.2023.110967

Methionine enkephalin inhibited cervical cancer migration as well as invasion and activated CD11b⁺ NCR1⁺ NKs of tumor microenvironment

Int Immunopharmacol. 2023 Nov;124(Pt B):110967. doi: 10.1016/j.intimp.2023.110967. Epub 2023 Sep 21.

Authors

Na Qu¹, Yiming Meng², Jingbo Zhai³, Noreen Griffin⁴, Yuanye Shan⁴, Yuhua Gao⁵, Fengping Shan⁶

Affiliations

¹ Department of Gynecological Radiotherapy Ward, Cancer Hospital of Dalian University of Technology (Liaoning Cancer Institute and Hospital), No. 44, Xiaoheyan Road, Shenyang 110042, Liaoning Province, China.
² Central Laboratory, Cancer Hospital of Dalian University of Technology (Liaoning Cancer Institute and Hospital), No. 44, Xiaoheyan Road, Shenyang 110042, Liaoning Province, China.
³ Key Laboratory of Zoonose Prevention and Control at Universities of Inner Mongolia Autonomous Region, Medical College, Inner Mongolia Minzu University, Tongliao 028000, China.
⁴ Biostax Inc. 1317 Edgewater Dr., Ste 4882, Orlando, FL 32804, USA.
⁵ Department of Gynecological Radiotherapy Ward, Cancer Hospital of Dalian University of Technology (Liaoning Cancer Institute and Hospital), No. 44, Xiaoheyan Road, Shenyang 110042, Liaoning Province, China. Electronic address: 52437438@qq.com.
⁶ Department of Immunology, School of Basic Medical Science, China Medical University, No. 77, Puhe Road, Shenyang 110122, Liaoning Province, China. Electronic address: fpshan@cmu.edu.cn.

PMID: 37741126
DOI: 10.1016/j.intimp.2023.110967

Abstract

This study was to study the role of methionine enkephalin (menk) in cell invasion and migration as well as NK cells activation of tumor microenvironment in cervical cancer. The results showed that menk inhibited cervical cancer migration and invasion. In addition, we found menk affected epithelial to mesenchymal transition (EMT) related indicators, with increasing E-cadherin level, decreasing N-cadherin and vimentin level. Through in vivo mouse model, we found that menk IFNγ and NKP46 expression was upregulated in tumor tissues by menk compared with controls, while LAG3 expression was inhibited by menk, besides, there was an upregulation of CD11b⁺ NCR1⁺ NKs of tumor microenvironment in cervical cancer. Therefore, we concluded that menk inhibited cancer migration and invasion via affecting EMT related indicators and activated CD11b⁺ NCR1⁺ NKs of tumor microenvironment in cervical cancer, laying a theoretical foundation for the further clinical treatment of menk.

Keywords: Cervical cancer; EMT; Invasion and migration; Menk; NKs.

MeSH terms

Animals
Cell Line, Tumor
Cell Movement
Enkephalin, Methionine / pharmacology
Epithelial-Mesenchymal Transition
Female
Humans
Mice
Natural Cytotoxicity Triggering Receptor 1
Tumor Microenvironment
Uterine Cervical Neoplasms* / drug therapy

Substances

Enkephalin, Methionine
Natural Cytotoxicity Triggering Receptor 1