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Detection of Canonical Hedgehog Signaling in Breast Cancer by 131-Iodine-Labeled Derivatives of the Sonic Hedgehog Protein

Authors :
David J. Yang
Izabela Tworowska
Richard Larson
Wendy A. Woodward
Lynn M. Opdenaker
Ning Tsao
Firas Mourtada
Jennifer Sims-Mourtada
Daniel L. Smith
Source :
Journal of Biomedicine and Biotechnology, Journal of Biomedicine and Biotechnology, Vol 2012 (2012)
Publication Year :
2012
Publisher :
Hindawi Publishing Corporation, 2012.

Abstract

Activation of hedgehog (HH) pathway signaling is observed in many tumors. Due to a feedback loop, the HH receptor Patched (PTCH-1) is overexpressed in tumors with activated HH signaling. Therefore, we sought to radiolabel the PTCH-1 ligand sonic (SHH) for detection of cancer cells with canonical HH activity. Receptor binding of131I-SHH was increased in cell lines with high HH pathway activation. Our findings also show that PTCH-1 receptor expression is decreased upon treatment with HH signaling inhibitors, and receptor binding of131I-SHH is significantly decreased following treatment with cyclopamine.In vivoimaging and biodistribution studies revealed significant accumulation of131I-SHH within tumor tissue as compared to normal organs. Tumor-to-muscle ratios were approximately 8 : 1 at 5 hours, while tumor to blood and tumor to bone were 2 : 1 and 5 : 1, respectively. Significant uptake was also observed in liver and gastrointestinal tissue. These studies show that131I-SHH is capable ofin vivodetection of breast tumors with high HH signaling. We further demonstrate that the hedgehog receptor PTCH-1 is downregulated upon treatment with hedgehog inhibitors. Our data suggests that radiolabeled SHH derivatives may provide a method to determine response to SHH-targeted therapies.

Details

Language :
English
ISSN :
11107251 and 11107243
Volume :
2012
Database :
OpenAIRE
Journal :
Journal of Biomedicine and Biotechnology
Accession number :
edsair.doi.dedup.....c7c68f3ee88d6fdd73d020b90f612a8d