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J Biomed Biotechnol. 2012;2012:639562. doi: 10.1155/2012/639562. Epub 2012 Jun 28.

Detection of canonical hedgehog signaling in breast cancer by 131-iodine-labeled derivatives of the sonic hedgehog protein.

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1
Helen F. Graham Cancer Center, Christiana Care Hospital, Newark, DE 19713, USA. jsimsmourtada@christianacare.org

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 of ¹³¹I-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 of ¹³¹I-SHH is significantly decreased following treatment with cyclopamine. In vivo imaging and biodistribution studies revealed significant accumulation of ¹³¹I-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 that ¹³¹I-SHH is capable of in vivo detection 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.

PMID:
22811598
PMCID:
PMC3395403
DOI:
10.1155/2012/639562
[Indexed for MEDLINE]
Free PMC Article
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