Neuromedin U secreted by colorectal cancer cells promotes a tumour-supporting microenvironment
Abstract Background Neuromedin U (NMU) was identified as one of the hub genes closely related to colorectal cancer (CRC) progression and was recently shown to be a motility inducer in CRC cells. Its autocrine signalling through specific receptors increases cancer cell migration and invasiveness. Bec...
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| Format: | Article |
| Language: | English |
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BMC
2022-12-01
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| Series: | Cell Communication and Signaling |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12964-022-01003-1 |
| _version_ | 1811188230382419968 |
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| author | Patrycja Przygodzka Kamila Soboska Ewelina Sochacka Marcin Pacholczyk Marcin Braun Hassan Kassassir Izabela Papiewska-Pająk Michal Kielbik Joanna Boncela |
| author_facet | Patrycja Przygodzka Kamila Soboska Ewelina Sochacka Marcin Pacholczyk Marcin Braun Hassan Kassassir Izabela Papiewska-Pająk Michal Kielbik Joanna Boncela |
| author_sort | Patrycja Przygodzka |
| collection | DOAJ |
| description | Abstract Background Neuromedin U (NMU) was identified as one of the hub genes closely related to colorectal cancer (CRC) progression and was recently shown to be a motility inducer in CRC cells. Its autocrine signalling through specific receptors increases cancer cell migration and invasiveness. Because of insufficient knowledge concerning NMU accessibility and action in the tumour microenvironment, its role in CRC remains poorly understood and its potential as a therapeutic target is still difficult to define. Methods NMU expression in CRC tissue was detected by IHC. Data from The Cancer Genome Atlas were used to analyse gene expression in CRC. mRNA and protein expression was detected by real-time PCR, immunoblotting or immunofluorescence staining and analysed using confocal microscopy or flow cytometry. Proteome Profiler was used to detect changes in the profiles of cytokines released by cells constituting tumour microenvironment after NMU treatment. NMU receptor activity was monitored by detecting ERK1/2 activation. Transwell cell migration, wound healing assay and microtube formation assay were used to evaluate the effects of NMU on the migration of cancer cells, human macrophages and endothelial cells. Results Our current study showed increased NMU levels in human CRC when compared to normal adjacent tissue. We detected a correlation between high NMUR1 expression and shorter overall survival of patients with CRC. We identified NMUR1 expression on macrophages, endothelial cells, platelets, and NMUR1 presence in platelet microparticles. We confirmed ERK1/2 activation by treatment of macrophages and endothelial cells with NMU, which induced pro-metastatic phenotypes of analysed cells and changed their secretome. Finally, we showed that NMU-stimulated macrophages increased the migratory potential of CRC cells. Conclusions We propose that NMU is involved in the modulation and promotion of the pro-metastatic tumour microenvironment in CRC through the activation of cancer cells and other tumour niche cells, macrophages and endothelial cells. Video abstract |
| first_indexed | 2024-04-11T14:16:05Z |
| format | Article |
| id | doaj.art-af77aad5869f4c03a78c7d79fa083911 |
| institution | Directory Open Access Journal |
| issn | 1478-811X |
| language | English |
| last_indexed | 2024-04-11T14:16:05Z |
| publishDate | 2022-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj.art-af77aad5869f4c03a78c7d79fa0839112022-12-22T04:19:25ZengBMCCell Communication and Signaling1478-811X2022-12-0120111710.1186/s12964-022-01003-1Neuromedin U secreted by colorectal cancer cells promotes a tumour-supporting microenvironmentPatrycja Przygodzka0Kamila Soboska1Ewelina Sochacka2Marcin Pacholczyk3Marcin Braun4Hassan Kassassir5Izabela Papiewska-Pająk6Michal Kielbik7Joanna Boncela8Institute of Medical Biology, Polish Academy of SciencesInstitute of Medical Biology, Polish Academy of SciencesInstitute of Medical Biology, Polish Academy of SciencesDepartment of Systems Biology and Engineering, Silesian University of TechnologyDepartment of Pathology, Medical University of LodzInstitute of Medical Biology, Polish Academy of SciencesInstitute of Medical Biology, Polish Academy of SciencesInstitute of Medical Biology, Polish Academy of SciencesInstitute of Medical Biology, Polish Academy of SciencesAbstract Background Neuromedin U (NMU) was identified as one of the hub genes closely related to colorectal cancer (CRC) progression and was recently shown to be a motility inducer in CRC cells. Its autocrine signalling through specific receptors increases cancer cell migration and invasiveness. Because of insufficient knowledge concerning NMU accessibility and action in the tumour microenvironment, its role in CRC remains poorly understood and its potential as a therapeutic target is still difficult to define. Methods NMU expression in CRC tissue was detected by IHC. Data from The Cancer Genome Atlas were used to analyse gene expression in CRC. mRNA and protein expression was detected by real-time PCR, immunoblotting or immunofluorescence staining and analysed using confocal microscopy or flow cytometry. Proteome Profiler was used to detect changes in the profiles of cytokines released by cells constituting tumour microenvironment after NMU treatment. NMU receptor activity was monitored by detecting ERK1/2 activation. Transwell cell migration, wound healing assay and microtube formation assay were used to evaluate the effects of NMU on the migration of cancer cells, human macrophages and endothelial cells. Results Our current study showed increased NMU levels in human CRC when compared to normal adjacent tissue. We detected a correlation between high NMUR1 expression and shorter overall survival of patients with CRC. We identified NMUR1 expression on macrophages, endothelial cells, platelets, and NMUR1 presence in platelet microparticles. We confirmed ERK1/2 activation by treatment of macrophages and endothelial cells with NMU, which induced pro-metastatic phenotypes of analysed cells and changed their secretome. Finally, we showed that NMU-stimulated macrophages increased the migratory potential of CRC cells. Conclusions We propose that NMU is involved in the modulation and promotion of the pro-metastatic tumour microenvironment in CRC through the activation of cancer cells and other tumour niche cells, macrophages and endothelial cells. Video abstracthttps://doi.org/10.1186/s12964-022-01003-1Colorectal cancerNeuromedin UNMU receptorsMacrophagesEndothelial cells |
| spellingShingle | Patrycja Przygodzka Kamila Soboska Ewelina Sochacka Marcin Pacholczyk Marcin Braun Hassan Kassassir Izabela Papiewska-Pająk Michal Kielbik Joanna Boncela Neuromedin U secreted by colorectal cancer cells promotes a tumour-supporting microenvironment Cell Communication and Signaling Colorectal cancer Neuromedin U NMU receptors Macrophages Endothelial cells |
| title | Neuromedin U secreted by colorectal cancer cells promotes a tumour-supporting microenvironment |
| title_full | Neuromedin U secreted by colorectal cancer cells promotes a tumour-supporting microenvironment |
| title_fullStr | Neuromedin U secreted by colorectal cancer cells promotes a tumour-supporting microenvironment |
| title_full_unstemmed | Neuromedin U secreted by colorectal cancer cells promotes a tumour-supporting microenvironment |
| title_short | Neuromedin U secreted by colorectal cancer cells promotes a tumour-supporting microenvironment |
| title_sort | neuromedin u secreted by colorectal cancer cells promotes a tumour supporting microenvironment |
| topic | Colorectal cancer Neuromedin U NMU receptors Macrophages Endothelial cells |
| url | https://doi.org/10.1186/s12964-022-01003-1 |
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