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.


METHODS
a-Ptch1 antibodies were raised against an oligo-peptide, designed according to the Ptch1 aminoacid sequence. The specificity of a-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
a-Ptch1 recognized a 160 kDa protein as shown by immunoblotting and cell surface staining of pancreatic cancer cells. Incubation with a-Ptch1 suppressed Hh signaling activity and proliferation of pancreatic cancer cells.


CONCLUSIONS
These results provide a new strategy for controling Hh dependent development of pancreatic cancer and other Hh related carcinomas.
Nakamura
Masafumi
M
Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. mnaka@surg1.med.kyushu-u.ac.jp
Kubo
Makoto
M
Yanai
Kosuke
K
Mikami
Yoshiko
Y
Ikebe
Mio
M
Nagai
Shuntaro
S
Yamaguchi
Koji
K
Tanaka
Masao
M
Katano
Mitsuo
M
D000906:Antibodies / Q000494:pharmacology*; D000918:Antibody Specificity; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface / Q000276:immunology* / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
D000906:Antibodies; D053823:Hedgehog Proteins; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface