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PMID: 12867593 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Alpha-galactosylceramide (KRN7000) suppression of chemical- and oncogene-dependent carcinogenesis.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 100 ·No. 16 ·2003-08-05 ·Pages 9464-9

Hayakawa Y, Rovero S, Forni G, Smyth MJ

Abstract

Recent studies have revealed significant efficacy of the marine sponge glycolipid, alpha-galactosylceramide (alpha-GalCer), in treatment of experimental metastatic cancers, infections, and autoimmune diseases. However, the capacity of alpha-GalCer to prevent tumor development had never, to our knowledge, been evaluated in mouse models of chemical- and oncogene-dependent carcinogenesis. In this study, we demonstrate that long-term administration of soluble alpha-GalCer, spanning the time of tumor initiation, inhibits primary tumor formation in three different models: methylcholanthrene-induced sarcomas, mammary carcinomas in Her-2/neu transgenic mice, and spontaneous sarcomas in p53-/- mice. Weekly treatment of mice with alpha-GalCer maintained lymphoid tissue natural killer cell and T cell activation and elevated serum IFN-gamma and IL-4 concentrations. Consistent with the antimetastatic activity of alpha-GalCer, prevention of methylcholanthrene-induced sarcoma was IFN-gammaand tumor necrosis factor-related apoptosis-inducing ligand dependent, but not perforin-dependent. Taken together, our results demonstrate that NK1.1+alphabetaTCR+ cell-based immune therapy can inhibit primary tumorigenesis.

MeSH Terms
Animals Antineoplastic Agents/pharmacology Apoptosis Dose-Response Relationship, Drug Enzyme-Linked Immunosorbent Assay Fibrosarcoma/metabolism Flow Cytometry Galactosylceramides/pharmacology Genes, p53 Humans Interferon-gamma/genetics Interleukin-12/metabolism Interleukin-4/metabolism Ligands Methylcholanthrene/pharmacology Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Transgenic Mutation Neoplasms/chemically induced,genetics,prevention & control Receptor, ErbB-2/genetics Time Factors Tumor Cells, Cultured Tumor Suppressor Protein p53/genetics
Chemicals
Antineoplastic Agents Galactosylceramides Ligands Tumor Suppressor Protein p53 Interleukin-12 Interleukin-4 Methylcholanthrene Interferon-gamma Receptor, ErbB-2 KRN 7000
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Hayakawa Yoshihiro
Cancer Immunology Program, Trescowthick Laboratories, Peter MacCallum Cancer Centre, Locked Bag 1, A'Beckett Street, Melbourne 8006, Australia.
Rovero Stefania
Forni Guido
Smyth Mark J
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.1630663100
Published
2003-08-05
Epub
2003-00-16
Pages
9464-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC170941
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.1630663100 PMC Full Text View journal details
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