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B7-H3 在乳腺癌中的表达及通过基因沉默上调 VEGF。

B7-H3 expression in breast cancer and upregulation of VEGF through gene silence.

机构信息

Suzhou Health College, Jiangsu Suzhou, People's Republic of China.

The Fourth Hospital of Suzhou, Jiangsu Suzhou, People's Republic of China.

出版信息

Onco Targets Ther. 2014 Oct 29;7:1979-86. doi: 10.2147/OTT.S63424. eCollection 2014.

DOI:10.2147/OTT.S63424
PMID:25378933
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4218908/
Abstract

B7-H3, a novel member of the B7 family, was previously known as a regulatory ligand regulating T-cell-mediated immune response, and in recent years it was found to take a significant role in various cancers. In some tumor types, high expression of B7-H3 had been linked to a poor prognosis, whereas in other cancers the opposite effect had been observed. The precise role of B7-H3 in tumor immunity is unclear, and further investigations are needed. In the present study, we studied the expression of B7-H3 in the pathologic specimens of 221 patients treated for breast cancer by immunohistochemistry. Strong B7-H3 expression was found in cancer tissues from 80.55% patients, and B7-H3 expression had a negative relation with vascular endothelial growth factor (VEGF) expression, microvascular density for CD34, and tumor size. Furthermore, through lipopolysaccharide-mediated delivery of stable short hairpin ribonucleic acid we observed that silencing of B7-H3 could increase the transcription and secreting of VEGF in breast cancer cell line MCF-7. In summary, the present study demonstrated that B7-H3 suppressed tumor growth through inhibiting VEGF expression. These results increased knowledge of the nonimmunological role of B7-H3 protein and provided novel insights into great biological functions and a putative therapeutic target in breast cancer.

摘要

B7-H3 是 B7 家族的一个新成员,以前被称为调节 T 细胞介导的免疫反应的调节配体,近年来,它在各种癌症中发挥了重要作用。在一些肿瘤类型中,B7-H3 的高表达与预后不良有关,而在其他癌症中则观察到相反的效果。B7-H3 在肿瘤免疫中的确切作用尚不清楚,需要进一步研究。在本研究中,我们通过免疫组织化学方法研究了 221 例乳腺癌患者病理标本中 B7-H3 的表达。在 80.55%的患者的癌组织中发现了强 B7-H3 表达,B7-H3 的表达与血管内皮生长因子(VEGF)表达、CD34 标记的微血管密度和肿瘤大小呈负相关。此外,通过脂多糖介导的稳定短发夹 RNA 的传递,我们观察到 B7-H3 的沉默可以增加乳腺癌细胞系 MCF-7 中 VEGF 的转录和分泌。总之,本研究表明 B7-H3 通过抑制 VEGF 表达抑制肿瘤生长。这些结果增加了对 B7-H3 蛋白非免疫作用的认识,并为乳腺癌的生物学功能和潜在治疗靶点提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a25/4218908/5f767c6b1a8e/ott-7-1979Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a25/4218908/98c6e3507ece/ott-7-1979Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a25/4218908/3656c5e10d11/ott-7-1979Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a25/4218908/dc6494c80f24/ott-7-1979Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a25/4218908/bce8c0f5e65e/ott-7-1979Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a25/4218908/5f767c6b1a8e/ott-7-1979Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a25/4218908/98c6e3507ece/ott-7-1979Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a25/4218908/3656c5e10d11/ott-7-1979Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a25/4218908/dc6494c80f24/ott-7-1979Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a25/4218908/bce8c0f5e65e/ott-7-1979Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a25/4218908/5f767c6b1a8e/ott-7-1979Fig5.jpg

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Oncol Lett. 2013 Nov;6(5):1253-1260. doi: 10.3892/ol.2013.1586. Epub 2013 Sep 13.
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MicroRNA-187, down-regulated in clear cell renal cell carcinoma and associated with lower survival, inhibits cell growth and migration though targeting B7-H3.
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Targeting CD276 for T cell-based immunotherapy of breast cancer.针对乳腺癌的基于 T 细胞的免疫治疗的 CD276 靶点。
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