實(shí)體瘤的生長(zhǎng)和轉(zhuǎn)移需要血管生成，以確保迅速分裂的腫瘤細(xì)胞能獲得充足的氧氣,、營養(yǎng)物質(zhì)和生長(zhǎng)因子。
血管內(nèi)皮生長(zhǎng)因子（VEGF）的轉(zhuǎn)錄因子是由HIF刺激調(diào)控的一個(gè)典型例子,?；熁蚍暖熌芤鹉[瘤組織的缺氧反應(yīng)，而血管內(nèi)皮生長(zhǎng)因子通過誘導(dǎo)血管生成促進(jìn)腫瘤的生長(zhǎng)和生存,，可見VEGF對(duì)腫瘤的生長(zhǎng)時(shí)至關(guān)重要的,，因此VEGF已成為一個(gè)誘人靶標(biāo)來治療中晚期腫瘤患者，具體表現(xiàn)在運(yùn)用一些VEGF的抗體來治療患者,。
近日,，發(fā)表在Exp Cell Res雜志上新研究證明信號(hào)素( Semaphorins)受到氧張力變化的影響也可能在腫瘤血管新生中起到關(guān)鍵作用，信號(hào)素原本在控制軸突生長(zhǎng)和調(diào)控免疫相關(guān)蛋白表達(dá)中發(fā)揮作用,。通過使用RNA干擾技術(shù),，在體外和體內(nèi)血管生成試驗(yàn)以及腫瘤異種移植實(shí)驗(yàn)中，研究人員證實(shí)信號(hào)素4D（SEMA4D）的表達(dá)受轉(zhuǎn)錄因子HIF家庭的控制下,，其與血管內(nèi)皮生長(zhǎng)因子一起聯(lián)合促進(jìn)腫瘤口腔鱗狀細(xì)胞癌（OSCC）的生長(zhǎng)和血管生成,。
使用封閉抗體信號(hào)素4D后，腫瘤生長(zhǎng)和血管生成都有所減少,，研究數(shù)據(jù)證實(shí)聯(lián)合針對(duì)VEGF和SEMA4D可能是一種新的抗血管生成治療口腔鱗狀細(xì)胞癌及其他實(shí)體瘤的新策略,。（生物谷：Bioon.com）
doi:10.1016/j.yexcr.2012.04.019
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PMID:
The hypoxia-inducible factor-responsive proteins semaphorin 4D and vascular endothelial growth factor promote tumor growth and angiogenesis in oral squamous cell carcinoma.
Zhou H, Yang YH, Binmadi NO, Proia P, Basile JR.
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.
