M2 Macrophage-Derived Exosomes Promote Cell Migration and Invasion in Colon Cancer
Published version of a preprint
Abstract
Clinical and experimental evidence has shown that tumor-associated macrophages promote cancer initiation and progression. However, the macrophage-derived molecular determinants that regulate colorectal cancer metastasis have not been fully characterized. Here, we demonstrate that M2 macrophage–regulated colorectal cancer cells' migration and invasion is dependent upon M2 macrophage–derived exosomes (MDE). MDE displayed a high expression level of miR-21-5p and miR-155-5p, and MDE-mediated colorectal cancer cells' migration and invasion depended on these two miRNAs. Mechanistically, miR-21-5p and miR-155-5p were transferred to colorectal cancer cells by MDE and bound to the BRG1 coding sequence, downregulating expression of BRG1, which has been identified as a key factor promoting the colorectal cancer metastasis, yet is downregulated in metastatic colorectal cancer cells. Collectively, these findings show that M2 macrophages induce colorectal cancer cells' migration and invasion and provide significant plasticity of BRG1 expression in response to tumor microenvironments during malignant progression. This dynamic and reciprocal cross-talk between colorectal cancer cells and M2 macrophages provides a new opportunity for the treatment of metastatic colorectal cancer. Significance: These findings report a functional role for miRNA-containing exosomes derived from M2 macrophages in regulating migration and invasion of colorectal cancer cells.
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“Other cellular components—for example, immune cells—play key roles in the evolution of a tumor (i.e., the presence of M2 macrophages accelerates tumor progression) [77,78,79,80].”
From The Tumor-on-Chip: Recent Advances in the Development of Microfluidic Systems to Recapitulate the Physiology of Solid Tumors (2019) · cites this paper as [79]
Cites
B lymphocytes secrete antigen-presenting vesicles.
Raposo, G., Nijman, H. W., Stoorvogel, W., Liejendekker, R., Harding, C. V., Melief, C. J., & Geuze, H. J. (1996) · The Journal of experimental medicine · doi:10.1084/jem.183.3.1161 · Cited by 3,546 · see citing works
Cancer-secreted miR-105 destroys vascular endothelial barriers to promote metastasis
Zhou, W., Fong, M. Y., Min, Y., Somlo, G., Liu, L., Palomares, M. R., Yu, Y., Chow, A., O’Connor, S. T. F., Chin, A. R., et al. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.03.007 · Cited by 1,476 · see citing works
Exosomes Mediate Stromal Mobilization of Autocrine Wnt-PCP Signaling in Breast Cancer Cell Migration
Luga, V., Zhang, L., Viloria-Petit, A. M., Ogunjimi, A. A., Inanlou, M. R., Chiu, E., Buchanan, M., Hosein, A. N., Basik, M., & Wrana, J. L. (2012) · Cell · doi:10.1016/j.cell.2012.11.024 · Cited by 1,311 · see citing works
Trophic macrophages in development and disease
Pollard, J. W. (2009) · Nature Reviews Immunology · doi:10.1038/nri2528 · Cited by 1,178 · see citing works
Macrophage polarization in pathology
Sica, A., Erreni, M., Allavena, P., & Porta, C. (2015) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-015-1995-y · Cited by 673 · see citing works
Ferraro, A., Kontos, C. K., Boni, T., Bantounas, I., Siakouli, D., Kosmidou, V., Vlassi, M., Spyridakis, Y., Tsipras, I., Zografos, G., et al. (2014) · Epigenetics · doi:10.4161/epi.26842 · Cited by 111 · see citing works
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Diversity, Mechanisms, and Significance of Macrophage Plasticity
Locati, M., Curtale, G., & Mantovani, A. (2020) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathmechdis-012418-012718 · Cited by 2,199 · see citing works
Exosomes: key players in cancer and potential therapeutic strategy
Dai, J., Su, Y., Zhong, S., Cong, L., Liu, B., Yang, J., Tao, Y., He, Z., Chen, C., & Jiang, Y. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00261-0 · Cited by 1,186 · see citing works
Yang, Q., Guo, N., Zhou, Y., Chen, J., Wei, Q., & Han, M. (2020) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2020.04.004 · Cited by 471 · see citing works
Tumor-associated macrophages: potential therapeutic strategies and future prospects in cancer
Li, C., Xu, X., Wei, S., Jiang, P., Xue, L., & Wang, J. (2021) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2020-001341 · Cited by 360 · see citing works
Self-citationWang, H., Tian, T., & Zhang, J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22168470 · Cited by 364 · see citing works
Colorectal liver metastasis: molecular mechanism and interventional therapy
Zhou, H., Liu, Z., Wang, Y., Wen, X., Amador, E. H., Yuan, L., Ran, X., Xiong, L., Ran, Y., Chen, W., et al. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00922-2 · Cited by 298 · see citing works
Trujillo-de Santiago, G., Flores-Garza, B. G., Tavares-Negrete, J. A., Lara-Mayorga, I. M., González-Gamboa, I., Zhang, Y. S., Rojas-Martínez, A., Ortiz-López, R., & Álvarez, M. M. (2019) · Materials · doi:10.3390/ma12182945 · Cited by 184 · see citing works
Emerging roles and therapeutic value of exosomes in cancer metastasis
Wu, M., Wang, G., Hu, W., Yao, Y., & Yu, X.-F. (2019) · Molecular Cancer · doi:10.1186/s12943-019-0964-8 · Cited by 140 · see citing works
Self-citationExosomal PD‐L1: New Insights Into Tumor Immune Escape Mechanisms and Therapeutic Strategies
Zhou, K., Guo, S., Li, F., Sun, Q., & Liang, G. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.569219 · Cited by 99 · see citing works
3D Immunocompetent Organ‐on‐a‐Chip Models
Maharjan, S., Cecen, B., & Zhang, Y. S. (2020) · Small Methods · doi:10.1002/smtd.202000235 · Cited by 62 · see citing works
Roles of Macrophages and Exosomes in Liver Diseases
Shen, M., Shen, Y., Fan, X., Men, R., Ye, T., & Yang, L. (2020) · Frontiers in Medicine · doi:10.3389/fmed.2020.583691 · Cited by 61 · see citing works
Comprehensive Analysis of Immune Implications and Prognostic Value of SPI1 in Gastric Cancer
Huang, J., Chen, W., Jie, Z., & Jiang, M. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.820568 · Cited by 38 · see citing works
HypoxaMIRs: Key Regulators of Hallmarks of Colorectal Cancer
Coronel-Hernández, J., Delgado-Waldo, I., Cantú de León, D., López-Camarillo, C., Jacobo-Herrera, N., Ramos-Payán, R., & Pérez-Plasencia, C. (2022) · Cells · doi:10.3390/cells11121895 · Cited by 13 · see citing works
- Authors
- Lan, J., Sun, L., Xu, F., Liu, L., Hu, F., Song, D., Hou, Z., Wu, W., Luo, X., Wang, J., Yuan, X., Hu, J., & Wang, G.
- Affiliations
- Tongji Hospital (CN)
- Huazhong University of Science and Technology (CN)
- Corresponding author
- Hu, Junbo
- Wang, Guihua
- ORCID
- Venue
- Cancer Research
- Published
- 2019-01-01
- Volume
- 79
- Issue
- 1
- Pages
- 146-158
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2900276526
- Cited by
- 643
- References
- 6
- Citations by year
- 2026: 35 · 2025: 67 · 2024: 91 · 2023: 117 · 2022: 114 · 2021: 120 · 2020: 68 · 2019: 30
- FWCI
- 19.51
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (NSFC) (81570525, 81773113, 81572725)
- 973 (2015CB553903-1)
- Huazhong University of Science and Technology (HUST) (540-5001540013)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Keywords
- M2 macrophages, exosomes, colorectal cancer, cell migration, cell invasion, miR-21-5p, miR-155-5p, SMARCA4, tumor microenvironment, metastasis, tumor-associated macrophages, microRNA transfer
- MeSH terms
- Cancer-Associated Fibroblasts, Animals, Cell Movement, DNA Helicases, Female, Follow-Up Studies, Humans, Lung Neoplasms, Macrophages, Male, Mice, Inbred BALB C, Mice, Nude, Neoplasm Invasiveness, Neoplasm Metastasis, Nuclear Proteins, Prognosis, Transcription Factors, Tumor Cells, Cultured, Biomarkers, Tumor, Colorectal Neoplasms, Gene Expression Regulation, Neoplastic, Survival Rate, Apoptosis, Xenograft Model Antitumor Assays, MicroRNAs, Cell Proliferation, Mice, Exosomes, Tumor Microenvironment
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