論文 - 詳細
| RRC ID | 86892 |
|---|---|
| 著者 | Oishi Y, Kawaai K, Tamura R, Kuroda Y, Noji S, Toda M, Matsuo K. |
| タイトル | Matrix Metalloproteinase-13 Is an Unfavorable Prognostic Factor in Chordoma by Digesting Growth Inhibitory Collagens. |
| ジャーナル | Cancer Med |
| Abstract |
OBJECTIVE:Chordomas are low-grade but invasive tumors with limited therapies. Some conventional chordomas exhibit cartilage-like extracellular matrix (ECM). This study examined the expression and clinical significance of collagenases in chordomas. METHODS:Brachyury-positive primary chordoma tissues were analyzed by immunohistochemistry for matrix metalloproteinase (MMP)13, MMP9, and cathepsin K, and by immunofluorescence for MMP13 and MMP9. ECM phenotype was categorized using safranin-O staining, where safranin-O marks cartilage-like ECM. We compared MMP13 expression scores and progression-free survival (PFS) between safranin-O-negative and -positive groups. Collagenase gene expression and protein localization in JHC7 cells were analyzed by quantitative PCR and immunocytochemistry, respectively. Collagen digestion activity was evaluated using fluorescein isothiocyanate-labeled type II collagen (COL2) in the presence or absence of an MMP13-specific inhibitor. Cell growth was evaluated in the presence of type I collagen (COL1) or COL2. RESULTS:Safranin-O negative chordomas had shorter PFS than safranin-O positive chordomas (p = 0.016). MMP13 was expressed in human chordoma tissues and JHC7 cells; the MMP13 expression score was higher in safranin-O-negative chordomas than in safranin-O-positive chordomas (p = 0.018). JHC7 cells digested COL2, and digestion was partially but significantly inhibited by an MMP13-specific inhibitor (p < 0.05). COL2 inhibited the growth of JHC7 cells more strongly than COL1 in a dose-dependent manner (p < 0.01). CONCLUSIONS:MMP13 may promote aggressive behavior in chordoma by degrading growth-inhibitory COL2-rich ECM. These data support MMP13 as a potential unfavorable prognostic marker and therapeutic target in chordoma. |
| 巻・号 | 15(2) |
| ページ | e71662 |
| 公開日 | 2026-2-1 |
| DOI | 10.1002/cam4.71662 |
| PMID | 41714307 |
| PMC | PMC12920066 |
| MeSH | Adult Aged Biomarkers, Tumor / metabolism Brachyury Protein Cell Line, Tumor Cell Proliferation Chordoma* / genetics Chordoma* / metabolism Chordoma* / mortality Chordoma* / pathology Collagen Type II* / metabolism Extracellular Matrix / metabolism Female Fetal Proteins / metabolism Humans Male Matrix Metalloproteinase 13* / genetics Matrix Metalloproteinase 13* / metabolism Middle Aged Prognosis T-Box Domain Proteins / metabolism |
| IF | 3.491 |
| リソース情報 | |
| ヒト・動物細胞 | HeLa(RCB0007) |