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Kinesin 26B modulates M2 polarization of macrophage by activating cancer-associated fibroblasts to aggravate gastric cancer occurrence and metastasis.
- Source :
-
World journal of gastroenterology [World J Gastroenterol] 2024 May 28; Vol. 30 (20), pp. 2689-2708. - Publication Year :
- 2024
-
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.<br />Aim: To investigate the regulatory functions of KIF26B on immune and metastasis of GC.<br />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.<br />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.<br />Conclusion: KIF26B regulated M2 polarization of macrophage through activating CAFs, regulating the occurrence and metastasis of GC.<br />Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.<br /> (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)
- Subjects :
- Animals
Female
Humans
Male
Mice
Cell Line, Tumor
Cell Movement
Epithelial-Mesenchymal Transition
Macrophages metabolism
Macrophages immunology
Mice, Inbred BALB C
Mice, Nude
Neoplasm Invasiveness
Neoplasm Metastasis
Neovascularization, Pathologic
Prognosis
Tumor Microenvironment
Tumor-Associated Macrophages metabolism
Tumor-Associated Macrophages immunology
Cancer-Associated Fibroblasts metabolism
Cancer-Associated Fibroblasts pathology
Gene Expression Regulation, Neoplastic
Kinesins metabolism
Kinesins genetics
Stomach Neoplasms pathology
Stomach Neoplasms metabolism
Stomach Neoplasms genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2219-2840
- Volume :
- 30
- Issue :
- 20
- Database :
- MEDLINE
- Journal :
- World journal of gastroenterology
- Publication Type :
- Academic Journal
- Accession number :
- 38855156
- Full Text :
- https://doi.org/10.3748/wjg.v30.i20.2689