Periostin directly and indirectly promotes tumor lymphangiogenesis of head and neck cancer.
Periostin directly and indirectly promotes tumor lymphangiogenesis of head and neck cancer.
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DOI：
10.1371/journal.pone.0044488
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Takata T
中科院分区：
文献类型：
--
作者：
Kudo Y;Iizuka S;Yoshida M;Nguyen PT;Siriwardena SB;Tsunematsu T;Ohbayashi M;Ando T;Hatakeyama D;Shibata T;Koizumi K;Maeda M;Ishimaru N;Ogawa I;Takata T
通过淋巴管转移到区域淋巴结在癌症进展中起关键作用。肿瘤淋巴管生成促进淋巴道转移，而血管内皮生长因子C（VEGF-C）是肿瘤淋巴管生成的重要激活因子。我们以前确定骨膜蛋白作为头颈部鳞状细胞癌（HNSCC）的侵袭和血管生成促进因子。在这项研究中，我们发现了骨膜蛋白在肿瘤淋巴管生成中的新作用。Periostin过表达上调HNSCC细胞中VEGF-C mRNA的表达。通过使用条件培养基从骨膜蛋白过表达HNSCC细胞，我们检查管形成的淋巴管内皮细胞。条件培养基从骨膜蛋白过表达细胞促进管形成。为了解periostin与VEGF-C的相关性，我们采用免疫组化方法对54例HNSCC中Periostin和VEGF-C的表达进行了比较。在HNSCC病例中，骨膜蛋白表达与VEGF-C表达相关性良好。此外，在HNSCC患者的血清中观察到骨膜蛋白和VEGF-C分泌之间的相关性。有趣的是，骨膜蛋白本身独立于VEGF-C促进淋巴管内皮细胞的管形成。骨膜素促进的淋巴管生成是由Src和Akt活性介导的。确实，在骨膜蛋白过度表达的异种移植肿瘤和HNSCC病例中观察到骨膜蛋白和淋巴状态之间可能的相关性。我们的研究结果表明，骨膜蛋白本身以及骨膜蛋白诱导的VEGF-C上调可能促进淋巴管生成。我们认为骨膜蛋白可能是预测HNSCC恶性行为的标志物，也可能是未来治疗干预的潜在靶点，以阻止HNSCC患者的肿瘤淋巴管浸润和淋巴管生成。
Metastasis to regional lymph nodes via lymphatic vessels plays a key role in cancer progression. Tumor lymphangiogenesis is known to promote lymphatic metastasis, and vascular endothelial growth factor C (VEGF-C) is a critical activator of tumor lymphangiogenesis during the process of metastasis. We previously identified periostin as an invasion- and angiogenesis-promoting factor in head and neck squamous cell carcinoma (HNSCC). In this study, we discovered a novel role for periostin in tumor lymphangiogenesis. Periostin overexpression upregulated VEGF-C mRNA expression in HNSCC cells. By using conditioned media from periostin-overexpressing HNSCC cells, we examined tube formation of lymphatic endothelial cells. Conditioned media from periostin-overexpressing cells promoted tube formation. To know the correlation between periostin and VEGF-C, we compared Periostin expression with VEGF-C expression in 54 HNSCC cases by immunohistochemistry. Periostin expression was correlated well with VEGF-C expression in HNSCC cases. Moreover, correlation between periostin and VEGF-C secretion was observed in serum from HNSCC patients. Interestingly, periostin itself promoted tube formation of lymphatic endothelial cells independently of VEGF-C. Periostin-promoted lymphangiogenesis was mediated by Src and Akt activity. Indeed possible correlation between periostin and lymphatic status in periostin-overexpressing xenograft tumors and HNSCC cases was observed. Our findings suggest that periostin itself as well as periostin-induced upregulation of VEGF-C may promote lymphangiogenesis. We suggest that periostin may be a marker for prediction of malignant behaviors in HNSCC and a potential target for future therapeutic intervention to obstruct tumoral lymphatic invasion and lymphangiogenesis in HNSCC patients.
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影响因子：
64.5
作者：
BROOKS, PC;MONTGOMERY, AMP;CHERESH, DA
通讯作者：
CHERESH, DA
影响因子：
4
作者：
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通讯作者：
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DOI：
10.1073/pnas.95.24.14389
发表时间：
1998-11-24
影响因子：
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通讯作者：
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影响因子：
50.3
作者：
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