The hypoxia-inducible factor-responsive proteins semaphorin 4D and vascular endothelial growth factor promote tumor growth and angiogenesis in oral squamous cell carcinoma.
The hypoxia-inducible factor-responsive proteins semaphorin 4D and vascular endothelial growth factor promote tumor growth and angiogenesis in oral squamous cell carcinoma.
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低氧诱导因子响应蛋白的信号素4D和血管内皮生长因子促进口服鳞状细胞癌的肿瘤生长和血管生成。
DOI：
10.1016/j.yexcr.2012.04.019
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发表时间：
2012-08-15
影响因子：
3.7
通讯作者：
Basile JR
中科院分区：
文献类型：
--
作者：
Zhou H;Yang YH;Binmadi NO;Proia P;Basile JR
实体瘤的生长和转移需要诱导血管生成，以确保向快速分裂的转化细胞输送氧气、营养素和生长因子。通过突变、细胞减少疗法产生的缺氧或当恶性肿瘤超出其血液供应时，肿瘤细胞经历从无血管表型到新生血管表型的变化，这是由转录调节因子的缺氧诱导因子（HIF）家族介导的转变。血管内皮生长因子（VEGF）是其转录受HIF刺激的基因的一个实例。VEGF在促进肿瘤生长和存活中起着至关重要的作用，其通过刺激新血管生长来响应诸如化疗或放疗诱导的缺氧的应激，因此其已成为中和抗体在治疗晚期肿瘤中的诱人靶点。新出现的证据表明，semaphorins，最初与轴突生长和免疫控制相关的蛋白质，也受到氧张力变化的调节，并可能在肿瘤诱导的血管生成中发挥作用。通过使用RNA干扰，在体外和体内的血管生成试验和肿瘤异种移植实验，我们证明，表达的semaphorin 4D（SEMA4D），这是在HIF家族的转录因子的控制下，协同VEGF，以促进肿瘤生长和血管在口腔鳞状细胞癌（OSCC）。我们使用阻断抗体来显示靶向SEMA4D功能沿着VEGF可以代表用于治疗OSCC和其他实体瘤的新的抗血管生成治疗策略。
Growth and metastasis of solid tumors requires induction of angiogenesis to ensure the delivery of oxygen, nutrients and growth factors to rapidly dividing transformed cells. Through either mutations, hypoxia generated by cytoreductive therapies, or when a malignancy outgrows its blood supply, tumor cells undergo a change from an avascular to a neovascular phenotype, a transition mediated by the hypoxia-inducible factor (HIF) family of transcriptional regulators. Vascular endothelial growth factor (VEGF) is one example of a gene whose transcription is stimulated by HIF. VEGF plays a crucial role in promoting tumor growth and survival by stimulating new blood vessel growth in response to such stresses as chemotherapy or radiotherapy-induced hypoxia, and it therefore has become a tempting target for neutralizing antibodies in the treatment of advanced neoplasms. Emerging evidence has shown that the semaphorins, proteins originally associated with control of axonal growth and immunity, are regulated by changes in oxygen tension as well and may play a role in tumor-induced angiogenesis. Through the use of RNA interference, in vitro and in vivo angiogenesis assays and tumor xenograft experiments, we demonstrate that expression of semaphorin 4D (SEMA4D), which is under the control of the HIF-family of transcription factors, cooperates with VEGF to promote tumor growth and vascularity in oral squamous cell carcinoma (OSCC). We use blocking antibodies to show that targeting SEMA4D function along with VEGF could represent a novel anti-angiogenic therapeutic strategy for the treatment of OSCC and other solid tumors.
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影响因子：
--
作者：
Fazzari P;Penachioni J;Gianola S;Rossi F;Eickholt BJ;Maina F;Alexopoulou L;Sottile A;Comoglio PM;Flavell RA;Tamagnone L
通讯作者：
Tamagnone L
影响因子：
3.3
作者：
Lin, Pin-Yi;Yu, Chuan-Hang;Chiang, Chun-Pin
通讯作者：
Chiang, Chun-Pin
影响因子：
6.2
作者：
Ch'ng, EweSeng;Tomita, Yasuhiko;Aozasa, Katsuyuki
通讯作者：
Aozasa, Katsuyuki
影响因子：
6
作者：
Guedez, L;Rivera, AM;Stetler-Stevenson, WG
通讯作者：
Stetler-Stevenson, WG
DOI：
10.1385/1-59259-750-5:255
发表时间：
2004-01-01
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Hannon, Gregory J;Conklin, Douglas S
通讯作者：
Conklin, Douglas S