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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1522181
This article is part of the Research Topic Community Series in Tumor Microenvironment and Metabolic Reprogramming in Cancer: Volume II View all 4 articles

The Role of the C5a-C5aR Pathway in Iron Metabolism and Gastric Cancer Progression

Provisionally accepted
Qinxue Ni Qinxue Ni 1*Hong Yang Hong Yang 2*Hang Rao Hang Rao 1*Liyong Zhang Liyong Zhang 1*Mengyuan Xiong Mengyuan Xiong 1*Xiao Han Xiao Han 2*Boshao Deng Boshao Deng 2*Lulu Wang Lulu Wang 2*Jian Chen Jian Chen 2*Yan Shi Yan Shi 1*
  • 1 Department of General Surgery, First Affiliated Hospital of Army Medical University, Chongqing, China
  • 2 Army Medical University, Chongqing, China

The final, formatted version of the article will be published soon.

    Gastric cancer continues to be a leading global health concern, with current therapeutic approaches requiring significant improvement. While the disruption of iron metabolism in the advancement of gastric cancer has been well-documented, the underlying regulatory mechanisms remain largely unexplored. Additionally, the complement C5a-C5aR pathway has been identified as a crucial factor in gastric cancer development.The impact of the complement system on iron metabolism and its role in gastric cancer progression is an area warranting further investigation. Our research demonstrates that the C5a-C5aR pathway promotes gastric cancer progression by enhancing iron acquisition in tumor cells through two mechanisms. First, it drives macrophage polarization toward the M2 phenotype, which has a strong iron-release capability.Second, it increases the expression of LCN2, a high-affinity iron-binding protein critical for iron export from tumor-associated macrophages, by activating endoplasmic reticulum stress in these cells. Both mechanisms facilitate the transfer of iron from macrophages to cancer cells, thereby promoting tumor cell proliferation. This study aims to elucidate the connection between the complement C5a-C5aR pathway and iron metabolism within the tumor microenvironment. Our data suggest a pivotal role of the C5a-C5aR pathway in tumor iron management, indicating that targeting its regulatory mechanisms may pave the way for future iron-targeted therapeutic approaches in cancer treatment.

    Keywords: C5a-C5aR pathway, gastric cancer, iron metabolism, Macrophage polarization, LCN2, ER stress 1.Introduction

    Received: 04 Nov 2024; Accepted: 23 Dec 2024.

    Copyright: © 2024 Ni, Yang, Rao, Zhang, Xiong, Han, Deng, Wang, Chen and Shi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Qinxue Ni, Department of General Surgery, First Affiliated Hospital of Army Medical University, Chongqing, China
    Hong Yang, Army Medical University, Chongqing, China
    Hang Rao, Department of General Surgery, First Affiliated Hospital of Army Medical University, Chongqing, China
    Liyong Zhang, Department of General Surgery, First Affiliated Hospital of Army Medical University, Chongqing, China
    Mengyuan Xiong, Department of General Surgery, First Affiliated Hospital of Army Medical University, Chongqing, China
    Xiao Han, Army Medical University, Chongqing, China
    Boshao Deng, Army Medical University, Chongqing, China
    Lulu Wang, Army Medical University, Chongqing, China
    Jian Chen, Army Medical University, Chongqing, China
    Yan Shi, Department of General Surgery, First Affiliated Hospital of Army Medical University, Chongqing, China

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