Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Apr 15, 2024; 16(4): 1479-1499
Published online Apr 15, 2024. doi: 10.4251/wjgo.v16.i4.1479
FAM53B promotes pancreatic ductal adenocarcinoma metastasis by regulating macrophage M2 polarization
Xuan-Zeng Pei, Min Cai, Da-Wei Jiang, Song-Hai Chen, Qing-Qing Wang, Hui-Min Lu, Yi-Fan Lu
Xuan-Zeng Pei, Min Cai, Da-Wei Jiang, Song-Hai Chen, Qing-Qing Wang, Yi-Fan Lu, Department of Hepatological Surgery, The First Hospital of Jiaxing, Jiaxing 314000, Zhejiang Province, China
Hui-Min Lu, Department of General Surgery, West China Hospital of Sichuan University, Chengdu 610044, Sichuan Province, China
Author contributions: Pei XZ wrote the manuscript; Cai M, Jiang DW, Chen SH, Wang QQ and Lu HM collected the data; Lu YF conceived and guided the study. All authors reviewed, edited, and approved the final manuscript and critically revised it for important intellectual content, gave final approval of the version to be published, and agreed to be accountable for all aspects of the work.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board at West China Hospital of Sichuan University.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the West China Hospital of Sichuan University.
Conflict-of-interest statement: The authors declare having no conflicts of interest.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at [email: luyifan927@163.com]. Participants gave informed consent for data sharing.
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 Non-Commercial (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: Yi-Fan Lu, PhD, Assistant Professor, Department of Hepatological Surgery, The First Hospital of Jiaxing, No. 1882 Zhonghuan South Road, Nanhu District, Jiaxing 314000, Zhejiang Province, China. luyifan927@163.com
Received: November 20, 2023
Peer-review started: November 20, 2023
First decision: December 26, 2023
Revised: January 8, 2024
Accepted: March 1, 2024
Article in press: March 1, 2024
Published online: April 15, 2024
Processing time: 142 Days and 20.4 Hours
ARTICLE HIGHLIGHTS
Research background

Our study investigates the role of FAM53B in regulating macrophage M2 polarization and its potential mechanisms in promoting pancreatic ductal adenocarcinoma (PDAC) metastasis.

Research motivation

The motivation for this study stems from a deep interest in the mechanisms of PDAC development and the critical role of macrophages in the tumor microenvironment. Given the highly aggressive nature of PDAC and its propensity to metastasize, we focused on exploring the underlying molecular mechanisms, with a particular focus on FAM53B's role in regulating macrophage M2 polarization. By further investigating the function of FAM53B, we expect to reveal its specific regulatory mechanisms during PDAC metastasis, providing a new perspective for an in-depth understanding of the development of this cancer.

Research objectives

To explore the role of FAM53B in the regulation of macrophage M2 polarization, further study the molecular mechanism that may be involved in promoting PDAC metastasis, and reveal the influence of FAM53B on the M2 polarization of macrophages, as well as the specific regulatory mechanism in PDAC metastasis.

Research methods

Various methods were used to investigate the role of FAM53B in regulating macrophage M2 polarization and promoting PDAC metastasis. A macrophage model regulated by FAM53B expression level was constructed by cell culture and gene knockout techniques. Subsequently, immunocytochemistry and coimmunoprecipitation techniques were used to detect M2 macrophage marker expression and the interaction between FAM53B and related proteins. In animal models, the effect of FAM53B on PDAC metastasis was evaluated by transplanting PDAC cell lines and observing tumor growth and metastasis. At the molecular level, transcriptomic and proteomic methods were used to analyze the changes in the FAM53B-regulated signaling pathway and related gene expression.

Research results

Our research showed that there was a significant increase in FAM53B levels in PDAC tissues, which was linked to the tumors' cancerous features. Experimental findings indicated that FAM53B can enhance macrophage M2 polarization, leading to an increased release of anti-inflammatory factors. The results from the mouse model further supported the role of FAM53B in PDAC metastasis, as blocking FAM53B stopped the tumor from spreading and invading other tissues.

Research conclusions

FAM53B promotes PDAC metastasis by regulating macrophage M2 polarization. This discovery could lead to new ways to treat PDAC.

Research perspectives

The results of this study are expected to provide a new molecular mechanism for in-depth understanding of the development and metastasis of PDAC and provide innovative ideas for the development of relevant therapeutic strategies. By revealing the key role of FAM53B in the regulation of macrophage M2 polarization, it can provide a basis for the design of targeted interventions. Further research could focus on developing FAM53B inhibitors or related therapeutic strategies to reduce the aggressiveness of PDAC and improve therapeutic efficacy. In addition, the interrelationships between FAM53B and other signaling pathways will be explored in depth to provide a more comprehensive understanding of the complex regulatory networks in the tumor microenvironment. This will provide important guidance for future clinical transformation and is expected to bring new breakthroughs in the treatment of PDAC patients.