Immunoprevention of basal cell carcinomas with recombinant hedgehog-interacting protein.
Basal cell carcinomas (BCCs) are driven by abnormal hedgehog signaling and highly overexpress several hedgehog target genes. We report here our use of one of these target genes, hedgehog-interacting protein (Hip1), as a tumor-associated antigen for immunoprevention of BCCs in Ptch1+/- mice treated with ionizing radiation. Hip1 mRNA is expressed in adult mouse tissues at levels considerably lower than those in BCCs. Immunization with either of two large recombinant Hip1 polypeptides was well tolerated in Ptch1+/- mice, induced B and T cell responses detectable by enzyme-linked immunosorbent assay, Western blot, delayed type hypersensitivity, and enzyme-linked immunospot assay, and reduced the number of BCCs by 42% (P < 0.001) and 32% (P < 0.01), respectively. We conclude that immunization with proteins specifically up-regulated by hedgehog signaling may hold promise as a preventive option for patients such as those with the basal cell nevus syndrome who are destined to develop large numbers of BCCs.
Vogt
Annika
A
Department of Dermatology, University of California San Francisco, 94143, USA.
Chuang
Pao-Tien
PT
Hebert
Jennifer
J
Hwang
Jimmy
J
Lu
Ying
Y
Kopelovich
Levy
L
Athar
Mohammad
M
Bickers
David R
DR
Epstein
Ervin H
EH
D000818:Animals; D015153:Blotting, Western; D002280:Basal Cell Carcinoma / Q000276:immunology* / Q000517:prevention & control; D004268:DNA-Binding Proteins / Q000276:immunology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D015972:Gene Expression Regulation, Neoplastic; D006652:Histological Techniques; D007114:Immunization; D051379:Mice; D008817:Mice, Mutant Strains; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology*; D018709:Statistics, Nonparametric; D013601:T-Lymphocytes / Q000276:immunology; D001616:beta-Galactosidase
D004268:DNA-Binding Proteins; C489536:Hip1 protein, mouse; D012333:RNA, Messenger; D001616:beta-Galactosidase