| First Author | O'Toole SA | Year | 2011 |
| Journal | Cancer Res | Volume | 71 |
| Issue | 11 | Pages | 4002-14 |
| PubMed ID | 21632555 | Mgi Jnum | J:172717 |
| Mgi Id | MGI:5008663 | Doi | 10.1158/0008-5472.CAN-10-3738 |
| Citation | O'Toole SA, et al. (2011) Hedgehog Overexpression Is Associated with Stromal Interactions and Predicts for Poor Outcome in Breast Cancer. Cancer Res 71(11):4002-4014 |
| abstractText | Hedgehog (Hh) signaling plays an important role in several malignancies but its clinical significance in breast cancer is unclear. In a cohort of 279 patients with invasive ductal carcinoma of the breast, expression of Hh ligand was significantly associated with increased risk of metastasis, breast cancer-specific death, and a basal-like phenotype. A paracrine signature, encompassing high epithelial Hh ligand and high stromal Gli1, was an independent predictor for overall survival in multivariate analysis. In 2 independent histological progression series (n = 301), Hh expression increased with atypia. Hh ligand overexpression in a mouse model of basal breast cancer increased growth, induced a poorly differentiated phenotype, accelerated metastasis, and reduced survival. A stromal requirement for these effects was supported by the lack of similar Hh-mediated changes in vitro, and by stromal-specific expression of Hh target genes in vivo. Furthermore, inhibition of Hh ligand with a monoclonal antibody (5E1) inhibited tumor growth and metastasis. These data suggest that epithelial-stromal Hh signaling, driven by ligand expression in carcinoma cells, promotes breast cancer growth and metastasis. Blockade of Hh signaling to peritumoral stromal cells may represent a novel therapeutic approach in some basal-like breast cancers. Cancer Res; 71(11); 4002-14. (c)2011 AACR. |
