Cancer apelin receptor suppresses vascular mimicry in malignant melanoma
Several reports indicate that apelin is often over-expressed in tumors, and therefore it has been suggested that the apelin–apelin receptor (APJ) system may induce tumor progression. In contrast, our previous research revealed high expression of the apelin–APJ system in tumor blood vessels, suggesti...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-01-01
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| Series: | Pathology and Oncology Research |
| Subjects: | |
| Online Access: | https://www.por-journal.com/articles/10.3389/pore.2023.1610867/full |
| _version_ | 1797218175803195392 |
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| author | Koichi Inukai Kazuyoshi Kise Yumiko Hayashi Weizhen Jia Fumitaka Muramatsu Naoki Okamoto Hirotaka Konishi Keigo Akuta Hiroyasu Kidoya Nobuyuki Takakura Nobuyuki Takakura Nobuyuki Takakura Nobuyuki Takakura |
| author_facet | Koichi Inukai Kazuyoshi Kise Yumiko Hayashi Weizhen Jia Fumitaka Muramatsu Naoki Okamoto Hirotaka Konishi Keigo Akuta Hiroyasu Kidoya Nobuyuki Takakura Nobuyuki Takakura Nobuyuki Takakura Nobuyuki Takakura |
| author_sort | Koichi Inukai |
| collection | DOAJ |
| description | Several reports indicate that apelin is often over-expressed in tumors, and therefore it has been suggested that the apelin–apelin receptor (APJ) system may induce tumor progression. In contrast, our previous research revealed high expression of the apelin–APJ system in tumor blood vessels, suggesting its involvement in the regulation of tumor vessel formation and normalization, resulting in the suppression of tumor growth by promoting the infiltration of T cells. Thus, the effect of the apelin–APJ system on tumors remains controversial. In this report, to clarify the effect of apelin in tumor cells, we analyzed the function of APJ in tumor cells using APJ knock out (KO) mice. In APJ-KO mice, Apelin overexpression in B16/BL6 (B16) melanoma cells induced greater tumor growth than controls. In an APJ-KO melanoma inoculation model, although angiogenesis is suppressed compared to wild type, no difference is evident in tumor growth. We found that APJ deficiency promoted vascular mimicry in tumors. In vitro, cultured APJ-KO B16 cells demonstrated a spindle-like shape. This phenotypic change was thought to be induced by epithelial–mesenchymal transition (EMT) based on evidence that APJ-KO B16 cells show persistently high levels of the mesenchymal maker, Zeb1; however, we found that EMT did not correlate with the transforming growth factor-β/smad signaling pathway in our model. We propose that apelin-APJ system in cancer cells induces tumor growth but negatively regulates EMT and tumor malignancy. |
| first_indexed | 2024-04-24T12:13:35Z |
| format | Article |
| id | doaj.art-6ae248833a1b4a64bf63218aed2a6e66 |
| institution | Directory Open Access Journal |
| issn | 1532-2807 |
| language | English |
| last_indexed | 2024-04-24T12:13:35Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Pathology and Oncology Research |
| spelling | doaj.art-6ae248833a1b4a64bf63218aed2a6e662024-04-08T09:32:20ZengFrontiers Media S.A.Pathology and Oncology Research1532-28072023-01-012910.3389/pore.2023.16108671610867Cancer apelin receptor suppresses vascular mimicry in malignant melanomaKoichi Inukai0Kazuyoshi Kise1Yumiko Hayashi2Weizhen Jia3Fumitaka Muramatsu4Naoki Okamoto5Hirotaka Konishi6Keigo Akuta7Hiroyasu Kidoya8Nobuyuki Takakura9Nobuyuki Takakura10Nobuyuki Takakura11Nobuyuki Takakura12Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, Suita, JapanDepartment of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, Suita, JapanDepartment of Integrative Vascular Biology, Faculty of Medical Sciences, University of Fukui, Fukui, JapanDepartment of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, Suita, JapanDepartment of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, Suita, JapanDepartment of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, Suita, JapanDepartment of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, Suita, JapanDepartment of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, Suita, JapanDepartment of Integrative Vascular Biology, Faculty of Medical Sciences, University of Fukui, Fukui, JapanDepartment of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, Suita, JapanWorld Premier Institute Immunology Frontier Research Center, Integrated Frontier Research for Medical Science Division, Osaka University, Suita, JapanInstitute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University, Suita, JapanCenter for Infectious Disease Education and Research, Osaka University, Suita, JapanSeveral reports indicate that apelin is often over-expressed in tumors, and therefore it has been suggested that the apelin–apelin receptor (APJ) system may induce tumor progression. In contrast, our previous research revealed high expression of the apelin–APJ system in tumor blood vessels, suggesting its involvement in the regulation of tumor vessel formation and normalization, resulting in the suppression of tumor growth by promoting the infiltration of T cells. Thus, the effect of the apelin–APJ system on tumors remains controversial. In this report, to clarify the effect of apelin in tumor cells, we analyzed the function of APJ in tumor cells using APJ knock out (KO) mice. In APJ-KO mice, Apelin overexpression in B16/BL6 (B16) melanoma cells induced greater tumor growth than controls. In an APJ-KO melanoma inoculation model, although angiogenesis is suppressed compared to wild type, no difference is evident in tumor growth. We found that APJ deficiency promoted vascular mimicry in tumors. In vitro, cultured APJ-KO B16 cells demonstrated a spindle-like shape. This phenotypic change was thought to be induced by epithelial–mesenchymal transition (EMT) based on evidence that APJ-KO B16 cells show persistently high levels of the mesenchymal maker, Zeb1; however, we found that EMT did not correlate with the transforming growth factor-β/smad signaling pathway in our model. We propose that apelin-APJ system in cancer cells induces tumor growth but negatively regulates EMT and tumor malignancy.https://www.por-journal.com/articles/10.3389/pore.2023.1610867/fullepithelial-mesenchymal transitionmelanomaapelinapelin receptorneovascularization |
| spellingShingle | Koichi Inukai Kazuyoshi Kise Yumiko Hayashi Weizhen Jia Fumitaka Muramatsu Naoki Okamoto Hirotaka Konishi Keigo Akuta Hiroyasu Kidoya Nobuyuki Takakura Nobuyuki Takakura Nobuyuki Takakura Nobuyuki Takakura Cancer apelin receptor suppresses vascular mimicry in malignant melanoma Pathology and Oncology Research epithelial-mesenchymal transition melanoma apelin apelin receptor neovascularization |
| title | Cancer apelin receptor suppresses vascular mimicry in malignant melanoma |
| title_full | Cancer apelin receptor suppresses vascular mimicry in malignant melanoma |
| title_fullStr | Cancer apelin receptor suppresses vascular mimicry in malignant melanoma |
| title_full_unstemmed | Cancer apelin receptor suppresses vascular mimicry in malignant melanoma |
| title_short | Cancer apelin receptor suppresses vascular mimicry in malignant melanoma |
| title_sort | cancer apelin receptor suppresses vascular mimicry in malignant melanoma |
| topic | epithelial-mesenchymal transition melanoma apelin apelin receptor neovascularization |
| url | https://www.por-journal.com/articles/10.3389/pore.2023.1610867/full |
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