據(jù)一項(xiàng)發(fā)表于Proceedings of National Academy of Sciences(PNAS)的研究報(bào)告稱,，研究人員發(fā)現(xiàn)一種能夠使血液凝固的蛋白質(zhì)——“選擇性剪切組織因子(alternatively spliced Tissue Factor, asTF)”對(duì)某些轉(zhuǎn)移性腫瘤的生長(zhǎng)起關(guān)鍵作用,。雖然身體的各個(gè)組織中都有asTF的存在，但該蛋白最主要還是存在與血管中,。該研究是首個(gè)報(bào)道選擇性剪切組織因子能夠促進(jìn)血管生成(angiogenesis)的研究報(bào)告,。
腫瘤血管生成是在原有的血管基礎(chǔ)上延伸擴(kuò)展而形成的新生毛細(xì)血管，這些新生血管為不斷侵潤(rùn)生長(zhǎng)的原發(fā)腫瘤提供營養(yǎng),，同時(shí)這些腫瘤新生毛細(xì)血管也可延伸轉(zhuǎn)移到其他組織中,。研究人員發(fā)現(xiàn)asTF能夠與內(nèi)皮細(xì)胞表面的整合素(integrins)結(jié)合，并誘導(dǎo)信號(hào)級(jí)聯(lián)引發(fā)血管生成,。血管生成能夠促進(jìn)細(xì)胞粘連(cell adhesion),，細(xì)胞遷移和新血管的生成，研究人員在人類宮頸癌中也發(fā)現(xiàn)asTF含量很高,。
據(jù)研究人員Bogdanov介紹,，該發(fā)現(xiàn)為科學(xué)家提供了一種全新的途徑研究組織因子基因影響組織形成過程，如血管生成,。由于在多種癌癥中組織因子基因的表達(dá)量較高,，因此研究人員希望可以利用該發(fā)現(xiàn)，針對(duì)各種特異性的組織因子找到一些能夠終止癌細(xì)胞生長(zhǎng)的方法,。（生物谷Bioon.com）
生物谷推薦原始出處：
PNAS October 29, 2009, doi: 10.1073/pnas.0905325106
Alternatively spliced tissue factor induces angiogenesis through integrin ligation
Y. W. van den Berga, L. G. van den Hengela, H. R. Myersa, O. Ayachia, E. Jordanovab, W. Rufc, C. A. Spekd, P. H. Reitsmaa, V. Y. Bogdanove and H. H. Versteega,1
aThe Einthoven Laboratory for Experimental Vascular Medicine and
bDepartment of Pathology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands;
cDepartment of Immunology and Microbial Science, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037;
dCenter for Experimental and Molecular Medicine, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands; and
eDivision of Hematology/Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, 3125 Eden Avenue, Cincinnati, OH 45267
The initiator of coagulation, full-length tissue factor (flTF), in complex with factor VIIa, influences angiogenesis through PAR-2. Recently, an alternatively spliced variant of TF (asTF) was discovered, in which part of the TF extracellular domain, the transmembrane, and cytoplasmic domains are replaced by a unique C terminus. Subcutaneous tumors produced by asTF-secreting cells revealed increased angiogenesis, but it remained unclear if and how angiogenesis is regulated by asTF. Here, we show that asTF enhances angiogenesis in matrigel plugs in mice, whereas a soluble form of flTF only modestly enhances angiogenesis. asTF dose-dependently upregulates angiogenesis ex vivo independent of either PAR-2 or VIIa. Rather, asTF was found to ligate integrins, resulting in downstream signaling. asTF-αVβ3 integrin interaction induces endothelial cell migration, whereas asTF-dependent formation of capillaries in vitro is dependent on α6β1 integrin. Finally, asTF-dependent aortic sprouting is sensitive to β1 and β3 integrin blockade and a TF-antibody that disrupts asTF-integrin interaction. We conclude that asTF, unlike flTF, does not affect angiogenesis via PAR-dependent pathways but relies on integrin ligation. These findings indicate that asTF may serve as a target to prevent pathological angiogenesis.
