Semaphorin7A promotes tumor growth and exerts a pro-angiogenic effect in macrophages of mammary tumor-bearing mice.
Semaphorin7A promotes tumor growth and exerts a pro-angiogenic effect in macrophages of mammary tumor-bearing mice.
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DOI：
10.3389/fphys.2014.00017
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发表时间：
2014
影响因子：
4
通讯作者：
Iragavarapu-Charyulu V
中科院分区：
文献类型：
--
作者：
Garcia-Areas R;Libreros S;Amat S;Keating P;Carrio R;Robinson P;Blieden C;Iragavarapu-Charyulu V
脑信号蛋白是神经系统发育过程中参与轴突导向的大家族分子，最近已显示具有血管生成和抗血管生成特性。脑信号蛋白7A（semaphorin 7A，SEMA 7A）在神经发生中具有趋化活性，并通过α1β 1整合素发挥免疫调节作用。SEMA 7A已显示促进单核细胞趋化性并诱导它们产生促炎介质。在这项研究中，我们探索了SEMA 7A在乳腺癌小鼠模型中的作用。我们表明，SEMA 7A是高度表达的DA-3小鼠乳腺肿瘤细胞相比，正常乳腺细胞（EpH 4），和腹腔引起的巨噬细胞从乳腺肿瘤荷瘤小鼠也表达SEMA 7A在更高的水平相比，那些来自正常小鼠。我们还表明，重组小鼠SEMA 7A处理的小鼠巨噬细胞显着增加其表达的促血管生成分子CXCL 2/MIP-2。SEMA 7A基因沉默可诱导DA-3荷瘤小鼠腹腔巨噬细胞CXCL 2/MIP-2表达降低。与野生型肿瘤相比，植入SEMA 7A沉默肿瘤细胞的小鼠显示肿瘤中血管生成减少。此外，与来自对照DA-3乳腺肿瘤的那些相比，来自携带SEMA 7A沉默肿瘤的小鼠的腹膜引发的巨噬细胞产生显著（p < 0.01）较低水平的血管生成蛋白，诸如CXCL 2/MIP-2、CXCL 1和MMP-9。我们推测，乳腺癌中的SEMA 7A可能使单核细胞偏斜成促肿瘤发生表型以支持肿瘤生长。SEMA 7A可能被证明在建立新的研究途径以揭示乳腺癌患者中重要的肿瘤-宿主免疫相互作用方面具有价值。
Semaphorins are a large family of molecules involved in axonal guidance during the development of the nervous system and have been recently shown to have both angiogenic and anti-angiogenic properties. Specifically, semaphorin 7A (SEMA7A) has been reported to have a chemotactic activity in neurogenesis and to be an immune modulator through α1β1integrins. SEMA7A has been shown to promote monocyte chemotaxis and induce them to produce proinflammatory mediators. In this study we explored the role of SEMA7A in a murine model of breast cancer. We show that SEMA7A is highly expressed by DA-3 murine mammary tumor cells in comparison to normal mammary cells (EpH4), and that peritoneal elicited macrophages from mammary tumor-bearing mice also express SEMA7A at higher levels compared to those derived from normal mice. We also show that murine macrophages treated with recombinant murine SEMA7A significantly increased their expression of proangiogenic molecule CXCL2/MIP-2. Gene silencing of SEMA7A in peritoneal elicited macrophages from DA-3 tumor-bearing mice resulted in decreased CXCL2/MIP-2 expression. Mice implanted with SEMA7A silenced tumor cells showed decreased angiogenesis in the tumors compared to the wild type tumors. Furthermore, peritoneal elicited macrophages from mice bearing SEMA7A-silenced tumors produce significantly (p < 0.01) lower levels of angiogenic proteins, such as CXCL2/MIP-2, CXCL1, and MMP-9, compared to those from control DA-3 mammary tumors. We postulate that SEMA7A in mammary carcinomas may skew monocytes into a pro-tumorigenic phenotype to support tumor growth. SEMA7A could prove to be valuable in establishing new research avenues toward unraveling important tumor-host immune interactions in breast cancer patients.
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影响因子：
4.4
作者：
Formolo, Catherine A.;Williams, Russell;Gordish-Dressman, Heather;MacDonald, Tobey J.;Lee, Norman H.;Hathout, Yetrib
通讯作者：
Hathout, Yetrib
影响因子：
20.3
作者：
Acevedo, Lisette M.;Barillas, Samuel;Cheresh, David A.
通讯作者：
Cheresh, David A.
影响因子：
3.7
作者：
Holvoet, S;Vincent, C;Serres, M
通讯作者：
Serres, M
DOI：
10.1084/jem.20061273
发表时间：
2007-05-14
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kang HR;Lee CG;Homer RJ;Elias JA
通讯作者：
Elias JA
影响因子：
16.2
作者：
Koppel, AM;Feiner, L;Raper, JA
通讯作者：
Raper, JA