瑞典醫(yī)科大學(xué)卡羅林斯卡研究所的研究人員利用模式動(dòng)物老鼠進(jìn)行研究,，發(fā)現(xiàn)一種可以阻斷腫瘤中血管形成從而終止腫瘤生長(zhǎng)的方法,，該研究或有助于開發(fā)新的癌癥治療藥物。這項(xiàng)研究發(fā)表在The Journal of Experimental Medicine雜志上,。
當(dāng)腫瘤生長(zhǎng)到豌豆粒大小時(shí),，癌細(xì)胞需要刺激形成新的血管，以此為腫瘤的生長(zhǎng)提供氧氣和營(yíng)養(yǎng)物質(zhì),，這一過(guò)程也稱為血管再生(angiogenesis),。目前科學(xué)家已經(jīng)開發(fā)了大量的血管再生抑制藥物，但這些藥物的效果都很有限,，因此,，需要開發(fā)出更有效的治療藥物。
在這項(xiàng)新的研究中,，研究人員對(duì)血管細(xì)胞表面一種ALK1受體進(jìn)行研究,，當(dāng)阻斷老鼠腫瘤中的ALK1受體時(shí)，發(fā)現(xiàn)血管再生受到抑制,，腫瘤停止生長(zhǎng),。ALK1受體可由信號(hào)蛋白TGF-β蛋白激活，研究表明,，TGF-β家族中兩種分子——TGF-β和BMP9可相互作用,，共同刺激腫瘤中血管再生。
ALK1受體途徑被阻斷,，其中一部分是由于遺傳原因,，另一部分原因是因?yàn)橐环N命名為RAP-041的藥物。研究人員認(rèn)為,，RAP-041可與其他血管再生抑制劑共同使用,，使對(duì)血管再生的抑制效果達(dá)到最大化。（生物谷Bioon.com）
生物谷推薦原始出處：
The Journal of Experimental Medicine January 11, 2010 doi:10.1084/jem.20091309
Genetic and pharmacological targeting of activin receptor-like kinase 1 impairs tumor growth and angiogenesis
Sara I. Cunha1, Evangelia Pardali2, Midory Thorikay2, Charlotte Anderberg1, Lukas Hawinkels2, Marie-José Goumans2, Jasbir Seehra3, Carl-Henrik Heldin4, Peter ten Dijke2, and Kristian Pietras1
1 Department of Medical Biochemistry and Biophysics, Division of Matrix Biology, Karolinska Institutet, Stockholm SE-171 77, Sweden
2 Department of Molecular Cell Biology and Centre for Biomedical Genetics, Leiden University Medical Center, Leiden 2300 RC, Netherlands
3 Acceleron Pharma, Cambridge, MA 02139
4 Ludwig Institute for Cancer Research, Uppsala University, Uppsala SE-751 05, Sweden
Members of the transforming growth factor β (TGF-β) family have been genetically linked to vascular formation during embryogenesis. However, contradictory studies about the role of TGF-β and other family members with reported vascular functions, such as bone morphogenetic protein (BMP) 9, in physiological and pathological angiogenesis make the need for mechanistic studies apparent. We demonstrate, by genetic and pharmacological means, that the TGF-β and BMP9 receptor activin receptor-like kinase (ALK) 1 represents a new therapeutic target for tumor angiogenesis. Diminution of ALK1 gene dosage or systemic treatment with the ALK1-Fc fusion protein RAP-041 retarded tumor growth and progression by inhibition of angiogenesis in a transgenic mouse model of multistep tumorigenesis. Furthermore, RAP-041 significantly impaired the in vitro and in vivo angiogenic response toward vascular endothelial growth factor A and basic fibroblast growth factor. In seeking the mechanism for the observed effects, we uncovered an unexpected signaling synergy between TGF-β and BMP9, through which the combined action of the two factors augmented the endothelial cell response to angiogenic stimuli. We delineate a decisive role for signaling by TGF-β family members in tumor angiogenesis and offer mechanistic insight for the forthcoming clinical development of drugs blocking ALK1 in oncology.
