MUC2 expression modulates immune infiltration in colorectal cancer
IntroductionColorectal cancer (CRC) is a prevalent malignancy with significant morbidity and mortality worldwide. A deeper understanding of the interaction of cancer cells with other cells in the tumor microenvironment is crucial to devise effective therapeutic strategies. MUC2, a major component of...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1500374/full |
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| author | Christophe M. Raynaud Ayesha Jabeen Eiman I. Ahmed Eiman I. Ahmed Satanay Hubrack Apryl Sanchez Shimaa Sherif Ahmad A. Al-Shaibi Bernice Lo Bernice Lo Jessica Roelands Davide Bedognetti Davide Bedognetti Wouter Hendrickx Wouter Hendrickx |
| author_facet | Christophe M. Raynaud Ayesha Jabeen Eiman I. Ahmed Eiman I. Ahmed Satanay Hubrack Apryl Sanchez Shimaa Sherif Ahmad A. Al-Shaibi Bernice Lo Bernice Lo Jessica Roelands Davide Bedognetti Davide Bedognetti Wouter Hendrickx Wouter Hendrickx |
| author_sort | Christophe M. Raynaud |
| collection | DOAJ |
| description | IntroductionColorectal cancer (CRC) is a prevalent malignancy with significant morbidity and mortality worldwide. A deeper understanding of the interaction of cancer cells with other cells in the tumor microenvironment is crucial to devise effective therapeutic strategies. MUC2, a major component of the protective mucus layer in the gastrointestinal tract, has been implicated in CRC progression and immune response regulation.MethodIn this study, we sought to elucidate the relationship between MUC2 expression and immune infiltration within CRC using in vitro models involving two well-established cell lines, HT-29 and LS-174T. By employing CRISPR-mediated MUC2 knockout, we investigated the influence of MUC2 on tumor immune infiltration and its interplay with T cells and NK cells enriched peripheral blood mononuclear cells (PBMCs) in 3D spheroid cultures.ResultsWhile MUC2 was more abundant in LS-174T cell line compared to HT-29, its knockout resulted in increased immune infiltration solely in the HT-29 cell line, but not in the LS-174T cell line. We revealed that the removal of MUC2 protein was compensated in LS-174T by the expression of other gel-forming mucin proteins (MUC6, MUC5B) commonly expressed in the gastrointestinal epithelium, while this was not observed in HT-29 cell line.ConclusionOur study is the first to demonstrate that MUC2 functions as a physical barrier to immune infiltration in colorectal cancer (CRC) in vitro. In HT-29 cells, MUC2 knockout increased immune infiltration, while in LS-174T cells, compensatory expression of other mucins (MUC6, MUC5B) maintained the barrier. These findings reveal the complexity of mucin biology in CRC and suggest that targeting mucin pathways could be a novel therapeutic approach. |
| format | Article |
| id | doaj-art-7fd191976db04f8fbd740a40e135992c |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-7fd191976db04f8fbd740a40e135992c2025-01-24T07:13:36ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011510.3389/fimmu.2024.15003741500374MUC2 expression modulates immune infiltration in colorectal cancerChristophe M. Raynaud0Ayesha Jabeen1Eiman I. Ahmed2Eiman I. Ahmed3Satanay Hubrack4Apryl Sanchez5Shimaa Sherif6Ahmad A. Al-Shaibi7Bernice Lo8Bernice Lo9Jessica Roelands10Davide Bedognetti11Davide Bedognetti12Wouter Hendrickx13Wouter Hendrickx14Tumor Biology and Immunology Laboratory, Research Branch, Sidra Medicine, Doha, QatarTumor Biology and Immunology Laboratory, Research Branch, Sidra Medicine, Doha, QatarTumor Biology and Immunology Laboratory, Research Branch, Sidra Medicine, Doha, QatarDepartment of Biomedical Science, College of Health Sciences, Qatar University, Doha, QatarLaboratory of immunoregulation, Research Branch, Sidra Medicine, Doha, QatarTumor Biology and Immunology Laboratory, Research Branch, Sidra Medicine, Doha, QatarTumor Biology and Immunology Laboratory, Research Branch, Sidra Medicine, Doha, QatarLaboratory of immunoregulation, Research Branch, Sidra Medicine, Doha, QatarLaboratory of immunoregulation, Research Branch, Sidra Medicine, Doha, QatarCollege of Health and Life Sciences (CHLS), Hamad bin Khalifa University (HBKU), Doha, QatarDepartment of Pathology, Leiden University Medical Center, Leiden, NetherlandsTumor Biology and Immunology Laboratory, Research Branch, Sidra Medicine, Doha, QatarClinical and Experimental Oncology and Hematology, Ospedale Policlinico San Martino, Genova, ItalyTumor Biology and Immunology Laboratory, Research Branch, Sidra Medicine, Doha, QatarDepartment of Pathology, Leiden University Medical Center, Leiden, NetherlandsIntroductionColorectal cancer (CRC) is a prevalent malignancy with significant morbidity and mortality worldwide. A deeper understanding of the interaction of cancer cells with other cells in the tumor microenvironment is crucial to devise effective therapeutic strategies. MUC2, a major component of the protective mucus layer in the gastrointestinal tract, has been implicated in CRC progression and immune response regulation.MethodIn this study, we sought to elucidate the relationship between MUC2 expression and immune infiltration within CRC using in vitro models involving two well-established cell lines, HT-29 and LS-174T. By employing CRISPR-mediated MUC2 knockout, we investigated the influence of MUC2 on tumor immune infiltration and its interplay with T cells and NK cells enriched peripheral blood mononuclear cells (PBMCs) in 3D spheroid cultures.ResultsWhile MUC2 was more abundant in LS-174T cell line compared to HT-29, its knockout resulted in increased immune infiltration solely in the HT-29 cell line, but not in the LS-174T cell line. We revealed that the removal of MUC2 protein was compensated in LS-174T by the expression of other gel-forming mucin proteins (MUC6, MUC5B) commonly expressed in the gastrointestinal epithelium, while this was not observed in HT-29 cell line.ConclusionOur study is the first to demonstrate that MUC2 functions as a physical barrier to immune infiltration in colorectal cancer (CRC) in vitro. In HT-29 cells, MUC2 knockout increased immune infiltration, while in LS-174T cells, compensatory expression of other mucins (MUC6, MUC5B) maintained the barrier. These findings reveal the complexity of mucin biology in CRC and suggest that targeting mucin pathways could be a novel therapeutic approach.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1500374/fullmucinsMUC2immune infiltrationspheroidscolon cancer |
| spellingShingle | Christophe M. Raynaud Ayesha Jabeen Eiman I. Ahmed Eiman I. Ahmed Satanay Hubrack Apryl Sanchez Shimaa Sherif Ahmad A. Al-Shaibi Bernice Lo Bernice Lo Jessica Roelands Davide Bedognetti Davide Bedognetti Wouter Hendrickx Wouter Hendrickx MUC2 expression modulates immune infiltration in colorectal cancer Frontiers in Immunology mucins MUC2 immune infiltration spheroids colon cancer |
| title | MUC2 expression modulates immune infiltration in colorectal cancer |
| title_full | MUC2 expression modulates immune infiltration in colorectal cancer |
| title_fullStr | MUC2 expression modulates immune infiltration in colorectal cancer |
| title_full_unstemmed | MUC2 expression modulates immune infiltration in colorectal cancer |
| title_short | MUC2 expression modulates immune infiltration in colorectal cancer |
| title_sort | muc2 expression modulates immune infiltration in colorectal cancer |
| topic | mucins MUC2 immune infiltration spheroids colon cancer |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1500374/full |
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