Anti-patched-1 antibodies suppress hedgehog signaling pathway and pancreatic cancer proliferation

Background: The hedgehog (Hh) signaling pathway is aberrantly activated in many human carcinomas including pancreatic cancer and regulates tumor cell growth. Overproduction of sonic hedgehog (Shh), a ligand of the Hh signaling pathway, increases the Hh signaling activity through transmitting the signal to patched-1 (Ptch1), the receptor of the Hh signaling pathway. Materials and Methods: α-Ptch1 antibodies were raised against an oligo-peptide, designed according to the Ptch1 amino-acid sequence. The specificity of α-Ptch1 was examined by immunoblotting and immuno-fluorescence, and biological effects were detected by RT-PCR and cell proliferation assay using two pancreatic cancer cell lines, Panc1 and SUIT-2. Results: α-Ptch1 recognized a 160 kDa protein as shown by immunoblotting and cell surface staining of pancreatic cancer cells. Incubation with α-Ptch1 suppressed Hh signaling activity and proliferation of pancreatic cancer cells. Conclusion: These results provide a new strategy for controling Hh dependent development of pancreatic cancer and other Hh related carcinomas.