Hedgehog (Hh)信号作用通道在发育中的胚胎中所起作用是，充当控制细胞增殖和细胞命运的网络的一部分。人们也曾发现它与几种固体肿瘤有关，在这些肿瘤中，它被认为直接调控肿瘤细胞增殖。
一项新的研究表明，Hedgehog在癌症中起一种很不相同的作用。由癌细胞分泌的Hedgehog配体，在肿瘤表皮细胞中未能激活信号作用，而是在“基质”（stroma）上发挥作用（“基质”由细胞外基质、成纤维细胞、内皮细胞和微血管组成，恶性细胞着床于其中）。该配体能够促进肿瘤生长，但显然是通过对肿瘤细胞微环境的一个效应来进行的。这些发现对于Hedgehog拮抗剂作为抗癌药物的应用具有重要意义。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
