Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 28, 2024; 30(20): 2689-2708
Published online May 28, 2024. doi: 10.3748/wjg.v30.i20.2689
Kinesin 26B modulates M2 polarization of macrophage by activating cancer-associated fibroblasts to aggravate gastric cancer occurrence and metastasis
Lian-Meng Huang, Ming-Jin Zhang
Lian-Meng Huang, Ming-Jin Zhang, Department of General Surgery, The 901st Hospital of PLA, Hefei 230031, Anhui Province, China
Author contributions: Huang LM contributed to conceptualization, writing original draft; Huang LM and Zhang MJ contributed to data curation, formal analysis, writing - review and editing.
Institutional review board statement: This study was approved by the Medical Ethics Committee of The 901st Hospital of PLA (No. 202311006). The written consent from each participant has been acquired.
Institutional animal care and use committee statement: All animal experiments were approved by the Animal Ethics Committee of Beijing Viewsolid Biotechnology Co. LTD (No. VS2126A00168).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The data that support the findings of this study are available from the corresponding author at zhangmingjin2001@163.com.
ARRIVE guidelines statement: The authors have read the ARRIVE Guidelines, and the manuscript was prepared and revised according to the ARRIVE Guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ming-Jin Zhang, MD, Professor, Department of General Surgery, The 901st Hospital of PLA, No. 424 Changjiang West Road, Shushan District, Hefei 230031, Anhui Province, China. zhangmingjin2001@163.com
Received: December 15, 2023
Revised: February 28, 2024
Accepted: April 19, 2024
Published online: May 28, 2024
Processing time: 164 Days and 6.5 Hours
Abstract
BACKGROUND

The regulatory effects of KIF26B on gastric cancer (GC) have been confirmed, but the specific mechanism still needs further exploration. Pan-cancer analysis shows that the KIF26B expression is highly related to immune infiltration of cancer-associated fibroblasts (CAFs), and CAFs promote macrophage M2 polarization and affect cancers’ progression.

AIM

To investigate the regulatory functions of KIF26B on immune and metastasis of GC.

METHODS

We analyzed genes’ mRNA levels by quantitative real-time polymerase chain reaction. Expression levels of target proteins were detected by immunohistochemistry, ELISA, and Western blotting. We injected AGS cells into nude mice for the establishment of a xenograft tumor model and observed the occurrence and metastasis of GC. The degree of inflammatory infiltration in pulmonary nodes was observed through hematoxylin-eosin staining. Transwell and wound healing assays were performed for the evaluation of cell invasion and migration ability. Tube formation assay was used for detecting angiogenesis. M2-polarized macrophages were estimated by immunofluorescence and flow cytometry.

RESULTS

KIF26B was significantly overexpressed in cells and tissues of GC, and the higher expression of KIF26B was related to GC metastasis and prognosis. According to in vivo experiments, KIF26B promoted tumor formation and metastasis of GC. KIF26B expression was positively associated with CAFs’ degree of infiltration. Moreover, CAFs could regulate M2-type polarization of macrophages, affecting GC cells’ migration, angiogenesis, invasion, and epithelial-mesenchymal transition process.

CONCLUSION

KIF26B regulated M2 polarization of macrophage through activating CAFs, regulating the occurrence and metastasis of GC.

Keywords: KIF26B; Gastric cancer; M2 polarization macrophage; Cancer-associated fibroblasts; Immunity; Metastasis

Core Tip:KIF26B could promote cancer-associated fibroblast activation, mediating macrophage M2 polarization and affecting the occurrence, lung metastasis, and abdominal metastasis of gastric cancer (GC). This study provides useful insights for exploring new mechanisms of GC and suppressing its progression.