Tumor Angiogenic Inhibition Triggered Necrosis (TAITN) in Oral Cancer
CXCR4 is a chemokine receptor crucial in tumor progression, although the angiogenic role of CXCR4 in oral squamous cell carcinoma (OSCC) has not been investigated. Here we show that CXCR4 is crucial for tumor angiogenesis, thereby supporting tumor survival in OSCC. Immunohistochemistry on human clin...
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MDPI AG
2019-07-01
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| Online Access: | https://www.mdpi.com/2073-4409/8/7/761 |
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| author | Saori Yoshida Hotaka Kawai Takanori Eguchi Shintaro Sukegawa May Wathone Oo Chang Anqi Kiyofumi Takabatake Keisuke Nakano Kuniaki Okamoto Hitoshi Nagatsuka |
| author_facet | Saori Yoshida Hotaka Kawai Takanori Eguchi Shintaro Sukegawa May Wathone Oo Chang Anqi Kiyofumi Takabatake Keisuke Nakano Kuniaki Okamoto Hitoshi Nagatsuka |
| author_sort | Saori Yoshida |
| collection | DOAJ |
| description | CXCR4 is a chemokine receptor crucial in tumor progression, although the angiogenic role of CXCR4 in oral squamous cell carcinoma (OSCC) has not been investigated. Here we show that CXCR4 is crucial for tumor angiogenesis, thereby supporting tumor survival in OSCC. Immunohistochemistry on human clinical specimens revealed that CXCR4 and a tumor vasculature marker CD34 were co-distributed in tumor vessels in human OSCC specimens. To uncover the effects of CXCR4 inhibition, we treated the OSCC-xenografted mice with AMD3100, so-called plerixafor, an antagonist of CXCR4. Notably, we found a unique pathophysiological structure defined as tumor angiogenic inhibition triggered necrosis (TAITN), which was induced by the CXCR4 antagonism. Treatment with AMD3100 increased necrotic areas with the induction of hypoxia-inducible factor-1α in the xenografted tumors, suggesting that AMD3100-induced TAITN was involved in hypoxia and ischemia. Taken together, we demonstrated that CXCR4 plays a crucial role in tumor angiogenesis required for OSCC progression, whereas TAITN induced by CXCR4 antagonism could be an effective anti-angiogenic therapeutic strategy in OSCC treatment. |
| first_indexed | 2024-03-12T19:31:07Z |
| format | Article |
| id | doaj.art-f6d2d7b5eff948cb980c4f38b763452f |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T19:31:07Z |
| publishDate | 2019-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-f6d2d7b5eff948cb980c4f38b763452f2023-08-02T04:36:48ZengMDPI AGCells2073-44092019-07-018776110.3390/cells8070761cells8070761Tumor Angiogenic Inhibition Triggered Necrosis (TAITN) in Oral CancerSaori Yoshida0Hotaka Kawai1Takanori Eguchi2Shintaro Sukegawa3May Wathone Oo4Chang Anqi5Kiyofumi Takabatake6Keisuke Nakano7Kuniaki Okamoto8Hitoshi Nagatsuka9Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, JapanDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, JapanDepartment of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, JapanDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, JapanDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, JapanDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, JapanDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, JapanDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, JapanDepartment of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, JapanDepartment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, JapanCXCR4 is a chemokine receptor crucial in tumor progression, although the angiogenic role of CXCR4 in oral squamous cell carcinoma (OSCC) has not been investigated. Here we show that CXCR4 is crucial for tumor angiogenesis, thereby supporting tumor survival in OSCC. Immunohistochemistry on human clinical specimens revealed that CXCR4 and a tumor vasculature marker CD34 were co-distributed in tumor vessels in human OSCC specimens. To uncover the effects of CXCR4 inhibition, we treated the OSCC-xenografted mice with AMD3100, so-called plerixafor, an antagonist of CXCR4. Notably, we found a unique pathophysiological structure defined as tumor angiogenic inhibition triggered necrosis (TAITN), which was induced by the CXCR4 antagonism. Treatment with AMD3100 increased necrotic areas with the induction of hypoxia-inducible factor-1α in the xenografted tumors, suggesting that AMD3100-induced TAITN was involved in hypoxia and ischemia. Taken together, we demonstrated that CXCR4 plays a crucial role in tumor angiogenesis required for OSCC progression, whereas TAITN induced by CXCR4 antagonism could be an effective anti-angiogenic therapeutic strategy in OSCC treatment.https://www.mdpi.com/2073-4409/8/7/761tumor blood vesseltumor angiogenic inhibition triggered necrosis (TAITN)CXCR4 antagonistoral squamous cell carcinomahypoxia |
| spellingShingle | Saori Yoshida Hotaka Kawai Takanori Eguchi Shintaro Sukegawa May Wathone Oo Chang Anqi Kiyofumi Takabatake Keisuke Nakano Kuniaki Okamoto Hitoshi Nagatsuka Tumor Angiogenic Inhibition Triggered Necrosis (TAITN) in Oral Cancer Cells tumor blood vessel tumor angiogenic inhibition triggered necrosis (TAITN) CXCR4 antagonist oral squamous cell carcinoma hypoxia |
| title | Tumor Angiogenic Inhibition Triggered Necrosis (TAITN) in Oral Cancer |
| title_full | Tumor Angiogenic Inhibition Triggered Necrosis (TAITN) in Oral Cancer |
| title_fullStr | Tumor Angiogenic Inhibition Triggered Necrosis (TAITN) in Oral Cancer |
| title_full_unstemmed | Tumor Angiogenic Inhibition Triggered Necrosis (TAITN) in Oral Cancer |
| title_short | Tumor Angiogenic Inhibition Triggered Necrosis (TAITN) in Oral Cancer |
| title_sort | tumor angiogenic inhibition triggered necrosis taitn in oral cancer |
| topic | tumor blood vessel tumor angiogenic inhibition triggered necrosis (TAITN) CXCR4 antagonist oral squamous cell carcinoma hypoxia |
| url | https://www.mdpi.com/2073-4409/8/7/761 |
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