Document Detail


Wnt and frizzled receptors as potential targets for immunotherapy in head and neck squamous cell carcinomas.
MedLine Citation:
PMID:  12242657     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The diverse receptor-ligand pairs of the Wnt and frizzled (Fz) families play important roles during embryonic development, and thus may be overexpressed in cancers that arise from immature cells. Hence, we investigated the expression and function of five Wnt (Wnt-1, 5a, 7a, 10b, 13) and two Fz (Fz-2, 5) genes in 10 head and neck squamous carcinoma cell lines (HNSCC). In comparison to normal bronchial or oral epithelial cells, all the HNSCC had markedly increased mRNA levels of Wnt-1, 7a, 10b, and 13, as well as Fz-2. Moreover, the levels of Wnt-1, 10b, and Fz-2 proteins were also markedly increased in HNSCC, relative to normal epithelial cells. Treatment of one HNSCC cell line (SNU 1076) with anti-Wnt-1 antibodies reduced the activity of the Wnt/Fz dependent transcription factor LEF/TCF, and diminished the expression of cyclin D1 and beta-catenin proteins. Blocking Wnt-1 signaling also inhibited proliferation and induced apoptosis in these cells. These results show that HNSCC cell lines often overexpress one or more Wnt and Fz genes, and suggest that the growth and survival of a subset of HNSCC may depend on the Wnt/Fz pathway. Hence, the Wnt and Fz receptors may be possible targets for immunotherapy therapy of this common cancer.
Authors:
Chae-Seo Rhee; Malini Sen; Desheng Lu; Christina Wu; Lorenzo Leoni; Jeffrey Rubin; Maripat Corr; Dennis A Carson
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Oncogene     Volume:  21     ISSN:  0950-9232     ISO Abbreviation:  Oncogene     Publication Date:  2002 Sep 
Date Detail:
Created Date:  2002-09-20     Completed Date:  2002-10-10     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  England    
Other Details:
Languages:  eng     Pagination:  6598-605     Citation Subset:  IM    
Affiliation:
Department of Medicine and The Sam and Rose Stein Institute for Research on Aging, University of California San Diego, La Jolla, California, CA 92093-0663, USA.
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MeSH Terms
Descriptor/Qualifier:
Antibodies / therapeutic use
Carcinoma, Squamous Cell / metabolism,  therapy*
Frizzled Receptors
Glycoproteins / analysis,  antagonists & inhibitors,  genetics
Head and Neck Neoplasms / metabolism,  therapy*
Humans
Immunotherapy
Intercellular Signaling Peptides and Proteins*
Proto-Oncogene Proteins / analysis,  antagonists & inhibitors*,  genetics
RNA, Messenger / analysis
Receptors, G-Protein-Coupled
Receptors, Neurotransmitter / analysis,  antagonists & inhibitors*,  genetics
Tumor Cells, Cultured
Wnt Proteins
Wnt1 Protein
Zebrafish Proteins*
Grant Support
ID/Acronym/Agency:
GM23200/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies; 0/FZD2 protein, human; 0/FZD5 protein, human; 0/Frizzled Receptors; 0/Fzd2 protein, mouse; 0/Glycoproteins; 0/Intercellular Signaling Peptides and Proteins; 0/Proto-Oncogene Proteins; 0/RNA, Messenger; 0/Receptors, G-Protein-Coupled; 0/Receptors, Neurotransmitter; 0/WNT1 protein, human; 0/WNT10B protein, human; 0/WNT2B protein, human; 0/WNT5A protein, human; 0/WNT7A protein, human; 0/Wnt Proteins; 0/Wnt1 Protein; 0/Wnt2b protein, mouse; 0/Wnt2b protein, rat; 0/Wnt7a protein, mouse; 0/Wnt7a protein, rat; 0/Zebrafish Proteins

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