DC-SIGN (CD209)-mediated interactions between bacteria, lung cancer tissues, and macrophages promote cancer metastasis

Abstract One of the hallmarks of lung cancers is the earlier metastasis resulting from the dissemination of cancer cells. Although accumulating evidence suggests that bacterial infection may be involved in the development of the metastasis of lung cancer, few studies have explored the molecular mech...

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Main Authors: Qiao Li, Nihal Hasan, Fei Zhao, Ying Xue, Sizhe Zhu, Yin Lv, Ling-yu Jiang, Kun Yang, Wenjin Li, Yingmiao Zhang, Yingxia He, Huahua Cai, Honghui Ding, John D. Klena, Andrey P. Anisimov, Shao-gang Wang, Hongxiang Chen, Chenglin Ye, Jingping Yuan, Tie Chen
Format: Article
Language:English
Published: BMC 2025-06-01
Series:Infectious Agents and Cancer
Subjects:
Online Access:https://doi.org/10.1186/s13027-025-00667-x
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author Qiao Li
Nihal Hasan
Fei Zhao
Ying Xue
Sizhe Zhu
Yin Lv
Ling-yu Jiang
Kun Yang
Wenjin Li
Yingmiao Zhang
Yingxia He
Huahua Cai
Honghui Ding
John D. Klena
Andrey P. Anisimov
Shao-gang Wang
Hongxiang Chen
Chenglin Ye
Jingping Yuan
Tie Chen
author_facet Qiao Li
Nihal Hasan
Fei Zhao
Ying Xue
Sizhe Zhu
Yin Lv
Ling-yu Jiang
Kun Yang
Wenjin Li
Yingmiao Zhang
Yingxia He
Huahua Cai
Honghui Ding
John D. Klena
Andrey P. Anisimov
Shao-gang Wang
Hongxiang Chen
Chenglin Ye
Jingping Yuan
Tie Chen
author_sort Qiao Li
collection DOAJ
description Abstract One of the hallmarks of lung cancers is the earlier metastasis resulting from the dissemination of cancer cells. Although accumulating evidence suggests that bacterial infection may be involved in the development of the metastasis of lung cancer, few studies have explored the molecular mechanisms of bacterial infection in the dissemination of lung cancer cells. A series of studies have indicated that certain Gram-negative bacteria are able to hijack antigen-presenting cells (APCs) via interaction with DC-SIGN (CD209) receptors to facilitate the dissemination of pathogens, including viruses, bacteria, fungi, and parasites. Therefore, in the present work, it was hypothesized that bacterial infection may promote the dissemination of cancer cells via the utilization of a similar mechanism. It was first discovered that human lung cancer tissues contain a very high diversity of bacterial DNAs, indicating the co-existence of lung cancer tissues and microbial organisms. It was then found that lung cancer tissues express DC-SIGN, leading to binding with a Gram-negative bacterium, Shigella sonnei. Further, this bacterium was found to be able not only to induce the expression of DC-SIGN on macrophages but also to enhance the migration ability of lung cancer cells in vitro. The in vivo experiments supported these observations, showing that in wild-type (WT) mice, Shigella sonnei infection significantly increased tumor size, weight, and metastatic nodules compared to SIGNR1 knockout (KO) mice. These observations were associated with increasing DC-SIGN expression in WT mice. Finally, these results suggest that bacterial infections could play a significant role in promoting lung cancer progression and metastasis via DC-SIGN-mediated mechanisms.
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spelling doaj-art-6221b1e9435444b3b51a27bab0b02e6f2025-08-20T03:22:48ZengBMCInfectious Agents and Cancer1750-93782025-06-0120111910.1186/s13027-025-00667-xDC-SIGN (CD209)-mediated interactions between bacteria, lung cancer tissues, and macrophages promote cancer metastasisQiao Li0Nihal Hasan1Fei Zhao2Ying Xue3Sizhe Zhu4Yin Lv5Ling-yu Jiang6Kun Yang7Wenjin Li8Yingmiao Zhang9Yingxia He10Huahua Cai11Honghui Ding12John D. Klena13Andrey P. Anisimov14Shao-gang Wang15Hongxiang Chen16Chenglin Ye17Jingping Yuan18Tie Chen19Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and TechnologyTongji Hospital, Tongji Medical College, Huazhong University of Sciences and TechnologyTongji Hospital, Tongji Medical College, Huazhong University of Sciences and TechnologyTongji Hospital, Tongji Medical College, Huazhong University of Sciences and TechnologyTongji Hospital, Tongji Medical College, Huazhong University of Sciences and TechnologyTongji Hospital, Tongji Medical College, Huazhong University of Sciences and TechnologyTongji Hospital, Tongji Medical College, Huazhong University of Sciences and TechnologyTongji Hospital, Tongji Medical College, Huazhong University of Sciences and TechnologyTongji Hospital, Tongji Medical College, Huazhong University of Sciences and TechnologyTongji Hospital, Tongji Medical College, Huazhong University of Sciences and TechnologyTongji Hospital, Tongji Medical College, Huazhong University of Sciences and TechnologyTongji Hospital, Tongji Medical College, Huazhong University of Sciences and TechnologyTongji Hospital, Tongji Medical College, Huazhong University of Sciences and TechnologyCenters for Disease Control and PreventionState Research Center for Applied Microbiology and BiotechnologyDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and TechnologyUnion Hospital, Tongji Medical College, Huazhong University of Sciences and TechnologyDepartment of Pathology, Renmin Hospital of Wuhan UniversityDepartment of Pathology, Renmin Hospital of Wuhan UniversityTongji Hospital, Tongji Medical College, Huazhong University of Sciences and TechnologyAbstract One of the hallmarks of lung cancers is the earlier metastasis resulting from the dissemination of cancer cells. Although accumulating evidence suggests that bacterial infection may be involved in the development of the metastasis of lung cancer, few studies have explored the molecular mechanisms of bacterial infection in the dissemination of lung cancer cells. A series of studies have indicated that certain Gram-negative bacteria are able to hijack antigen-presenting cells (APCs) via interaction with DC-SIGN (CD209) receptors to facilitate the dissemination of pathogens, including viruses, bacteria, fungi, and parasites. Therefore, in the present work, it was hypothesized that bacterial infection may promote the dissemination of cancer cells via the utilization of a similar mechanism. It was first discovered that human lung cancer tissues contain a very high diversity of bacterial DNAs, indicating the co-existence of lung cancer tissues and microbial organisms. It was then found that lung cancer tissues express DC-SIGN, leading to binding with a Gram-negative bacterium, Shigella sonnei. Further, this bacterium was found to be able not only to induce the expression of DC-SIGN on macrophages but also to enhance the migration ability of lung cancer cells in vitro. The in vivo experiments supported these observations, showing that in wild-type (WT) mice, Shigella sonnei infection significantly increased tumor size, weight, and metastatic nodules compared to SIGNR1 knockout (KO) mice. These observations were associated with increasing DC-SIGN expression in WT mice. Finally, these results suggest that bacterial infections could play a significant role in promoting lung cancer progression and metastasis via DC-SIGN-mediated mechanisms.https://doi.org/10.1186/s13027-025-00667-xLung cancerMetastasisDC-SIGNGram-negative bacteria
spellingShingle Qiao Li
Nihal Hasan
Fei Zhao
Ying Xue
Sizhe Zhu
Yin Lv
Ling-yu Jiang
Kun Yang
Wenjin Li
Yingmiao Zhang
Yingxia He
Huahua Cai
Honghui Ding
John D. Klena
Andrey P. Anisimov
Shao-gang Wang
Hongxiang Chen
Chenglin Ye
Jingping Yuan
Tie Chen
DC-SIGN (CD209)-mediated interactions between bacteria, lung cancer tissues, and macrophages promote cancer metastasis
Infectious Agents and Cancer
Lung cancer
Metastasis
DC-SIGN
Gram-negative bacteria
title DC-SIGN (CD209)-mediated interactions between bacteria, lung cancer tissues, and macrophages promote cancer metastasis
title_full DC-SIGN (CD209)-mediated interactions between bacteria, lung cancer tissues, and macrophages promote cancer metastasis
title_fullStr DC-SIGN (CD209)-mediated interactions between bacteria, lung cancer tissues, and macrophages promote cancer metastasis
title_full_unstemmed DC-SIGN (CD209)-mediated interactions between bacteria, lung cancer tissues, and macrophages promote cancer metastasis
title_short DC-SIGN (CD209)-mediated interactions between bacteria, lung cancer tissues, and macrophages promote cancer metastasis
title_sort dc sign cd209 mediated interactions between bacteria lung cancer tissues and macrophages promote cancer metastasis
topic Lung cancer
Metastasis
DC-SIGN
Gram-negative bacteria
url https://doi.org/10.1186/s13027-025-00667-x
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