Suzhou Health College, Jiangsu Suzhou, People's Republic of China.
The Fourth Hospital of Suzhou, Jiangsu Suzhou, People's Republic of China.
Onco Targets Ther. 2014 Oct 29;7:1979-86. doi: 10.2147/OTT.S63424. eCollection 2014.
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.
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。