論文 - 詳細
| RRC ID | 52005 |
|---|---|
| 著者 | Kanemaru A, Yamamoto K, Kawaguchi M, Fukushima T, Lin CY, Johnson MD, Camerer E, Kataoka H. |
| 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. |
| ジャーナル | Int J Cancer |
| Abstract |
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. |
| 巻・号 | 140(1) |
| ページ | 130-141 |
| 公開日 | 2017-1-1 |
| DOI | 10.1002/ijc.30426 |
| PMID | 27615543 |
| MeSH | Adult Aged Aged, 80 and over Cancer-Associated Fibroblasts / pathology* Carcinoma, Squamous Cell / genetics Carcinoma, Squamous Cell / metabolism Carcinoma, Squamous Cell / pathology* Cell Line, Tumor Cell Movement / drug effects Cells, Cultured Culture Media, Conditioned / pharmacology Culture Media, Serum-Free / pharmacology Female Gene Expression Regulation, Neoplastic Gene Knockdown Techniques Humans Male Membrane Proteins / metabolism* Middle Aged Mouth Neoplasms / genetics Mouth Neoplasms / metabolism Mouth Neoplasms / pathology* Paracrine Communication Proteinase Inhibitory Proteins, Secretory / genetics* Receptor, PAR-2 / metabolism* Serine Endopeptidases / metabolism* |
| IF | 5.145 |
| 引用数 | 17 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | NB1RGB(RCB0222) |