The role of semaphorin 4D in tumor development and angiogenesis in human breast cancer.
The role of semaphorin 4D in tumor development and angiogenesis in human breast cancer.
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DOI：
10.2147/ott.s114708
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发表时间：
2016
影响因子：
4
通讯作者：
Dong J
中科院分区：
文献类型：
--
作者：
Jiang H;Chen C;Sun Q;Wu J;Qiu L;Gao C;Liu W;Yang J;Jun N;Dong J
Semaphorin 4D（Sema 4D）在某些类型的肿瘤中高度表达，并在调节肿瘤血管生成和生长中起作用。然而，目前还不清楚Sema 4D在乳腺癌中的作用。本研究旨在探讨Sema 4D对乳腺癌细胞增殖、细胞周期进程、凋亡、侵袭、迁移、肿瘤生长和血管生成的影响。通过蛋白质印迹分析研究Sema 4D在MCF 10A、184 A1、HCC 1937、MDA-MB-468、MDA-MB-231、Hs 578 T、BT474、MCF-7和T47 D乳腺癌细胞系中的表达水平。通过用慢病毒编码的Sema 4D短发夹RNA（shRNA）或Sema 4D感染建立Sema 4D下调或过表达。采用MTT法、流式细胞术、创伤愈合实验、transwell实验等方法，观察Sema 4D对MDA-MB-231和MDA-MB-468细胞增殖、细胞周期进程、凋亡、侵袭和迁移的影响。裸鼠皮下注射MDA-MB-231细胞，分别用慢病毒载体Sema 4D、Sema 4D shRNA和GFP感染，检测肿瘤血管生成。Sema 4D在乳腺癌细胞系中的表达水平高于正常人乳腺上皮细胞系，尤其是在MDA-MB-231和MDA-MB-468细胞中。Sema 4D下调可明显抑制MDA-MB-231和MDA-MB-468细胞的增殖能力，而G 0/G1期细胞比例和凋亡细胞比例增加。此外，这些细胞的侵袭和迁移能力明显降低。当体内用慢病毒编码的Sema 4D shRNA感染时，异种移植物生长以及血管生成被抑制。Sema 4D表达下调对MDA-MB-231和MDA-MB-468细胞的增殖能力、侵袭、迁移和凋亡均有明显影响。慢病毒介导的Sema 4D shRNA感染BALB/c裸鼠后，肿瘤生长和血管生成明显受到抑制。我们的研究结果表明，Sema 4D可能代表一种新的治疗靶点，为人类乳腺癌。
Semaphorin 4D (Sema4D) is highly expressed in certain types of tumors and functions in the regulation of tumor angiogenesis and growth. However, it is still not clear regarding the roles of Sema4D in breast cancer. This study was designed to explore the effects of Sema4D on proliferation, cell cycle progression, apoptosis, invasion, migration, tumor growth, and angiogenesis in breast cancer. The expression level of Sema4D was investigated in MCF10A, 184A1, HCC1937, MDA-MB-468, MDA-MB-231, Hs578T, BT474, MCF-7, and T47D breast cancer cell lines by Western blotting analysis. Sema4D downregulation or overexpression was established by infection with lentiviruses-encoding Sema4D short hairpin RNA (shRNA) or Sema4D. To evaluate the effects of Sema4D on cell proliferation, cell cycle progression, apoptosis, invasion, and migration of MDA-MB-231 and MDA-MB-468 cells, methods including MTT assay, flow cytometry, wound healing assay, and transwell experiments were applied. BALB/c nude mice were injected with MDA-MB-231 cells, which were respectively infected with lentiviruses-encoding Sema4D, Sema4D shRNA, and GFP, followed by tumor angiogenesis assay. Sema4D was expressed at higher levels in breast cancer cell lines compared with the normal human breast epithelial cell lines, especially in MDA-MB-231 and MDA-MB-468 cells. Cell proliferation ability was remarkably inhibited in Sema4D downregulated condition, whereas the proportions of cells in the G0/G1 phase and apoptosis increased in MDA-MB-231 and MDA-MB-468 cells. In addition, the invasion and migration abilities of these cells were obviously reduced. Xenograft growth as well as angiogenesis was inhibited when infected with lentiviruses-encoding Sema4D shRNA in vivo. Downregulation of Sema4D had notable influence on cell proliferation ability, invasion, migration, and apoptosis of both MDA-MB-231 and MDA-MB-468 cells. Furthermore, infection with lentiviruses-encoding Sema4D shRNA obviously inhibited tumor growth and angiogenesis in BALB/c nude mice. Our results showed that Sema4D may represent a novel therapeutic target for human breast cancer.