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Deregulated matriptase activity in oral squamous cell carcinoma promotes the infiltration of cancer-associated fibroblasts by paracrine activation of protease-activated receptor 2
http://hdl.handle.net/10458/6185
http://hdl.handle.net/10458/61859e9b608d-c54a-4ac4-9235-c45c962cd5f1
| 名前 / ファイル | ライセンス | アクション |
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学位論文要旨 (11.6 MB)
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学位論文審査結果の要旨 (206.5 kB)
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本文 (52.2 kB)
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| アイテムタイプ | 学位論文 / Thesis or Dissertation(1) | |||||
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| 公開日 | 2020-06-21 | |||||
| タイトル | ||||||
| タイトル | Deregulated matriptase activity in oral squamous cell carcinoma promotes the infiltration of cancer-associated fibroblasts by paracrine activation of protease-activated receptor 2 | |||||
| 言語 | en | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||
| 資源タイプ | doctoral thesis | |||||
| アクセス権 | ||||||
| アクセス権 | open access | |||||
| 著者 |
金丸, 愛
× 金丸, 愛× Kanemaru, Ai× Yamamoto, Koji× Kawaguchi, Makiko× Fukushima, Tsuyoshi× Lin, Chen-Yong× Michael, D. Johnson× Eric, Camerer× Kataoka, Hiroaki |
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| 出版者 | Wiley | |||||
| 言語 | en | |||||
| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Cancer-associated fibroblasts (CAFs) are known to contribute to cancer progression. We have reported that cell surface expression of hepatocyte growth factor activator inhibitor 1 (HAI-1) is decreased in invasive oral squamous cell carcinoma (OSCC) cells. This study examined if HAI-1-insufficiency contributes to CAF recruitment in OSCC. Serum-free conditioned medium (SFCM) from a human OSCC line (SAS) stimulated the migration of 3 human fibroblast cell lines, NB1RGB, MRC5 and KD. SFCM from HAI-1-knockdown SAS showed an additive effect on the migration of NB1RGB and MRC5, but not KD. SAS SFCM induced protease-activated receptor-2 (PAR-2) expression in NB1RGB and MRC5, but not in KD, and a PAR-2 antagonist blocked the stimulatory effect of HAI-1 knockdown on migration of the PAR-2 expressing cell lines. Moreover, HAI-1-deficient SFCM showed additive stimulatory effects on the migration of wild-type but not PAR-2-deficient mouse fibroblasts. Therefore, the enhanced migration induced by HAI-1-insufficiency was mediated by PAR-2 activation in fibroblasts. This activation resulted from the deregulation of the activity of matriptase, a PAR-2 agonist protease. HAI-1 may thus prevent CAF recruitment to OSCC by controlling matriptase activity. When HAI-1 expression is reduced on OSCC, matriptase may contribute to CAF accumulation by paracrine activation of fibroblast PAR-2. Immunohistochemical analysis of resected OSCC revealed increased PAR2-positive CAFs in 35% (33/95) of the cases studied. The increased PAR-2 positive CAFs tended to correlate with infiltrative histology of the invasion front and shorter disease-free survival of the patients. | |||||
| 言語 | en | |||||
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| 値 | 以下に掲載:International Journal of Cancer .2017, Volume140, Issue 1, pp 130-141, doi:http://dx.doi.org/10.1002/ijc.30426 | |||||
| 内容記述 | ||||||
| 言語 | ja | |||||
| 学位名 | ||||||
| 学位名 | 博士(医学) | |||||
| 言語 | ja | |||||
| 学位授与機関 | ||||||
| 学位授与機関識別子Scheme | kakenhi | |||||
| 学位授与機関識別子 | 17601 | |||||
| 学位授与機関名 | 宮崎大学 | |||||
| 言語 | ja | |||||
| 学位授与年月日 | ||||||
| 学位授与年月日 | 2017-03-24 | |||||
| 学位授与番号 | ||||||
| 学位授与番号 | 甲第50号 | |||||
| 関連サイト | ||||||
| 識別子タイプ | HDL | |||||
| 関連識別子 | http://hdl.handle.net/10458/6184 | |||||
| 言語 | en | |||||
| 関連名称 | http://hdl.handle.net/10458/6184 | |||||
| 著者版フラグ | ||||||
| 出版タイプ | VoR | |||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
