Regulatory role of methionine enkephalin in myeloid-derived suppressor cells and macrophages in human cutaneous squamous cell carcinoma.

Bai, X ; Shan, F ; et al.

In: International immunopharmacology, Jg. 99 (2021-10-01), S. 107996

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The antitumor effects of methionine enkephalin (MENK), also known as opioid growth factor (OGF), including its inhibitory effects on cutaneous squamous cell carcinoma (CSCC), have been established. In this study, we determined the precise mechanism by which MENK suppresses CSCC cell growth. In particular, MENK induced G0/G1 cell cycle arrest and promoted apoptosis in CSCC cells via the Bcl-2/Bax/Caspase-3 signaling pathway. Moreover, MENK reduced immunosuppression by downregulating the number of myeloid-derived suppressor cells (MDSCs) and regulating the polarization of tumor-associated macrophages from M2 to M1 in vivo. Furthermore, JAK2/STAT3, an important tumor-promotion and immunosuppression signaling pathway that is involved in MDSC expansion in tumors and macrophage polarization, was inhibited. These findings highlight the potential of the JAK2/STAT3 signaling pathway as a therapeutic target and suggest the clinical application of MENK for CSCC.

Titel:	Regulatory role of methionine enkephalin in myeloid-derived suppressor cells and macrophages in human cutaneous squamous cell carcinoma.
Autor/in / Beteiligte Person:	Bai, X ; Shan, F ; Qu, N ; Huang, H ; Handley, M ; Griffin, N ; Zhang, S ; Cao, X
Link:	Zum Volltext
Zeitschrift:	International immunopharmacology, Jg. 99 (2021-10-01), S. 107996
Veröffentlichung:	Amsterdam ; New York : Elsevier Science, c2001-, 2021
Medientyp:	academicJournal
ISSN:	1878-1705 (electronic)
DOI:	10.1016/j.intimp.2021.107996
Schlagwort:	Animals Apoptosis drug effects Apoptosis Regulatory Proteins drug effects Cell Cycle drug effects Cell Line, Tumor Cell Polarity drug effects Cell Proliferation drug effects Cytokines metabolism Enkephalin, Methionine genetics Female Humans Immunosuppression Therapy Janus Kinase 2 metabolism Mice, Inbred BALB C Mice, Nude RNA, Small Interfering STAT3 Transcription Factor metabolism Signal Transduction drug effects Mice Carcinoma, Squamous Cell drug therapy Enkephalin, Methionine metabolism Enkephalin, Methionine pharmacology Macrophages drug effects Myeloid-Derived Suppressor Cells drug effects
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Int Immunopharmacol] 2021 Oct; Vol. 99, pp. 107996. <i>Date of Electronic Publication: </i>2021 Jul 23. MeSH Terms: Carcinoma, Squamous Cell / drug therapy ; Enkephalin, Methionine / metabolism ; Enkephalin, Methionine / pharmacology ; Macrophages / drug effects ; Myeloid-Derived Suppressor Cells / *drug effects ; Animals ; Apoptosis / drug effects ; Apoptosis Regulatory Proteins / drug effects ; Cell Cycle / drug effects ; Cell Line, Tumor ; Cell Polarity / drug effects ; Cell Proliferation / drug effects ; Cytokines / metabolism ; Enkephalin, Methionine / genetics ; Female ; Humans ; Immunosuppression Therapy ; Janus Kinase 2 / metabolism ; Mice, Inbred BALB C ; Mice, Nude ; RNA, Small Interfering ; STAT3 Transcription Factor / metabolism ; Signal Transduction / drug effects ; Mice Contributed Indexing: Keywords: Apoptosis; MDSCs; MENK; Macrophage; OGFr; STAT3 Substance Nomenclature: 0 (Apoptosis Regulatory Proteins) ; 0 (Cytokines) ; 0 (RNA, Small Interfering) ; 0 (STAT3 Transcription Factor) ; 58569-55-4 (Enkephalin, Methionine) ; EC 2.7.10.2 (Janus Kinase 2) Entry Date(s): Date Created: 20210726 Date Completed: 20220131 Latest Revision: 20240226 Update Code: 20240226

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