Journal
BIOMED RESEARCH INTERNATIONAL
Volume 2014, Issue -, Pages -Publisher
HINDAWI LTD
DOI: 10.1155/2014/525680
Keywords
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Funding
- National Institutes of Health [U54-GM104941]
- NIH/National Cancer Institute [RO1 CA138230-01]
- National Institute of General Medical Sciences-NIGMS [8 P20 GM103446-13]
- Delaware INBRE program
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High tumor hedgehog expression is correlated with poor prognosis in invasive ductal carcinoma. Peptides which bind the patched receptor have recently been reported to have a growth inhibitory effect in tumors with activated hedgehog signaling. We sought to examine growth inhibition with these peptides in breast cancer cells and use these peptides as molecular imaging probes to follow changes in hedgehog expression after chemotherapy. Significant growth inhibition was observed in breast cancer cell lines treated with PTCH-blocking peptides. Significant in vitro uptake was observed with both FITC- and Tc-99m-EC-peptide conjugates. In vivo imaging studies displayed greater accumulation of Tc-99m-labeled peptides within tumors as compared to adjacent muscle tissue. Patched receptor expression increased after treatment and this correlated with an increase in tumor radiotracer uptake. These studies suggest that peptides which bind the sonic hedgehog docking site in patched receptor correlate with patched expression and can be used to image patched in vivo. Further, our data suggest that radiolabeled peptides may enable us to examine the activity of the hedgehog signaling pathway and to evaluate response to anti-cancer therapies.
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