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- W2325087785 abstract "Hedgehog (Hh) signalling plays an important role in a number of malignancies, yet its clinical significance in breast cancer is unclear. In a cohort of 279 patients with invasive ductal carcinoma (IDC) of the breast, we found that expression of Hh ligand was associated with increased risk of metastasis, breast cancer specific death and the 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 two 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 pheno-type, 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 tumour growth and metastasis. These data suggest epithelial-stromal Hh signalling, driven by ligand expression in carcinoma cells, promotes breast cancer growth and metastasis. Blockade of Hh ligand activity may represent a novel therapeutic approach in metastatic breast cancer." @default.
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- W2325087785 date "2012-01-01" @default.
- W2325087785 modified "2023-09-22" @default.
- W2325087785 title "35. Hedgehog overexpression is regulated by stromal interactions and predicts for poor outcome in invasive ductal carcinoma" @default.
- W2325087785 doi "https://doi.org/10.1016/s0031-3025(16)32927-0" @default.
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