| Item type |
デフォルトアイテムタイプ_（フル）(1) |
| 公開日 |
2023-03-18 |
| タイトル |
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タイトル |
Roles of VEGF-Flt-1 signaling in malignant behaviors of oral squamous cell carcinoma |
|
言語 |
en |
| 作成者 |
Subarnbhesaj, Ajiravudh
Miyauchi, Mutsumi
Chanbora, Chea
Mikuriya, Aki
Nguyen, Phuong Thao
Furusho, Hisako
Ayuningtyas, Nurina Febriyanti
Fujita, Minoru
Toratani, Shigeaki
Takechi, Masaaki
Niida, Shumpei
Takata, Takashi
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| アクセス権 |
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アクセス権 |
open access |
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アクセス権URI |
http://purl.org/coar/access_right/c_abf2 |
| 権利情報 |
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権利情報 |
2017 Subarnbhesaj et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| 内容記述 |
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内容記述 |
Background: Vascular endothelial growth factor (VEGF) is a highly specific signaling protein for vascular endothelial cells that plays a critical role in tumor growth and invasion through angiogenesis, and may contribute to cell migration and activation of pre-osteoclasts, osteoclasts and some tumor cells. Objectives: We aimed to clarify the detailed roles of VEGF-Flt-1 signaling in bone invasion of oral squamous cell carcinoma (OSCC) cells. Results: Forty-two (42) of 54 cases with gingival SCC (77.8%) strongly expressed VEGF, and had a significantly increased number of Flt-1+ osteoclasts (p<0.01) and more aggressive bone invasion (p<0.05). PlGF, a ligand of Flt-1, induced osteoclastogenesis in single culture of bone marrow cells (BMCs), and inhibition of Flt-1-signaling by VEGF tyrosine kinase inhibitor and It’s down stream (Akt and ERK1/2) inhibitos reduced osteoclastogenesis in PlGF-stimulated BMCs (p<0.01). In molecular level, PlGF stimulation significantly upregulated RANKL expression in Flt-1-expressing HSC2 cells via phosphorylation of Akt and ERK1/2. In the co-culture of VEGF-producing HSC2 cells and BMCs, number of TRAP-positive osteoclasts markedly increased (p<0.01). The osteoclastogenesis was significantly inhibited by RANKL-neutralizing antibody (p<0.01) as well as by VEGF tyrosine kinase inhibitor (p<0.01) and it’s downstream (Akt and ERK1/2) inhibitors (p<0.01, p<0.05, respectively). Conclusion: VEGF-Flt-1 signaling induces osteoclastogenesis in OSCC through two possible ways: 1) VEGF produced from OSCC cells can directly stimulate the Flt-1 pathway in preosteoclasts to induce migration to future bone resorbing area and differentiation into osteoclasts, and 2) VEGF-Flt-1 signaling upregulates RANKL expression in OSCC cells, which indirectly leads to osteoclast differentiation. Therefore, blocking of the VEGF-Flt-1 signaling may help inhibit bone invasion of OSCC. |
|
言語 |
en |
| 内容記述 |
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内容記述タイプ |
Other |
|
内容記述 |
This work was supported by Grants-in-Aid for scientific research (A) from the Ministry of Education, Science and Culture (#21249088 [T.T.]). |
| 出版者 |
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出版者 |
Public Library of Science |
| 言語 |
|
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言語 |
eng |
| 資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
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資源タイプ |
journal article |
| 出版タイプ |
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|
出版タイプ |
VoR |
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出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| 関連情報 |
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|
識別子タイプ |
DOI |
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|
関連識別子 |
10.1371/journal.pone.0187092 |
| 関連情報 |
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|
識別子タイプ |
PMID |
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関連識別子 |
29149180 |
| 関連情報 |
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|
識別子タイプ |
DOI |
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|
関連識別子 |
https://doi.org/10.1371/journal.pone.0187092 |
| 収録物識別子 |
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収録物識別子タイプ |
ISSN |
|
収録物識別子 |
1932-6203 |
| 開始ページ |
|
|
開始ページ |
e0187092 |
| 書誌情報 |
PLoS ONE
PLoS ONE
巻 12,
号 11,
p. e0187092,
発行日 2017-11-17
|
| 旧ID |
48681 |
PLoSOne_12_11_ e0187092.pdf (12.0 MB)
