Hedgehog (Hh)信號作用通道在發(fā)育中的胚胎中所起作用是,，充當控制細胞增殖和細胞命運的網(wǎng)絡的一部分,。人們也曾發(fā)現(xiàn)它與幾種固體腫瘤有關,，在這些腫瘤中,，它被認為直接調(diào)控腫瘤細胞增殖,。
一項新的研究表明,，Hedgehog在癌癥中起一種很不相同的作用,。由癌細胞分泌的Hedgehog配體,，在腫瘤表皮細胞中未能激活信號作用，而是在“基質(zhì)”（stroma）上發(fā)揮作用（“基質(zhì)”由細胞外基質(zhì),、成纖維細胞,、內(nèi)皮細胞和微血管組成,，惡性細胞著床于其中）。該配體能夠促進腫瘤生長,，但顯然是通過對腫瘤細胞微環(huán)境的一個效應來進行的,。這些發(fā)現(xiàn)對于Hedgehog拮抗劑作為抗癌藥物的應用具有重要意義。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature 455, 406-410 (18 September 2008) | doi:10.1038/nature07275
A paracrine requirement for hedgehog signalling in cancer
Robert L. Yauch1,3, Stephen E. Gould1,3, Suzie J. Scales1, Tracy Tang1, Hua Tian1, Christina P. Ahn1, Derek Marshall1, Ling Fu1, Thomas Januario1, Dara Kallop1, Michelle Nannini-Pepe1, Karen Kotkow2,4, James C. Marsters1, Lee L. Rubin2,4 & Frederic J. de Sauvage1
1 Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA
2 Curis Inc., 45 Moulton Street, Cambridge, Massachusetts 02138, USA
3 These authors contributed equally to this work.
4 Present address: Harvard Stem Cell Institute, Harvard University, Biolabs Room 1065, 16 Divinity Avenue, Cambridge, Massachusetts 02138, USA.
Ligand-dependent activation of the hedgehog (Hh) signalling pathway has been associated with tumorigenesis in a number of human tissues1, 2, 3, 4,5, 6, 7. Here we show that, although previous reports have described a cell-autonomous role for Hh signalling in these tumours1, 2, 3, 4, 5, 6, 7, Hh ligands fail to activate signalling in tumour epithelial cells. In contrast, our data support ligand-dependent activation of the Hh pathway in the stromal microenvironment. Specific inhibition of Hh signalling using small molecule inhibitors, a neutralizing anti-Hh antibody or genetic deletion of smoothened (Smo) in the mouse stroma results in growth inhibition in xenograft tumour models. Taken together, these studies demonstrate a paracrine requirement for Hh ligand signalling in the tumorigenesis of Hh-expressing cancers and have important implications for the development of Hh pathway antagonists in cancer.
