Inhibition of the hedgehog pathway targets the tumor-associated stroma in pancreatic cancer.

ABSTRACT:

Purpose

The Hedgehog (Hh) pathway has emerged as an important pathway in multiple tumor types and is thought to be dependent on a paracrine signaling mechanism. The purpose of this study was to determine the role of pancreatic cancer-associated fibroblasts (human pancreatic stellate cells, HPSCs) in Hh signaling. In addition, we evaluated the efficacy of a novel Hh antagonist, AZD8542, on tumor progression with an emphasis on the role of the stroma compartment.

Experimental design

Expression of Hh pathway members and activation of the Hh pathway were analyzed in both HPSCs and pancreatic cancer cells. We tested the effects of Smoothened (SMO) inhibition with AZD8542 on tumor growth in vivo using an orthotopic model of pancreatic cancer containing varying amounts of stroma.

SUBMITTER: Hwang RF 

PROVIDER: S-EPMC3685283 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature