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PMID: 18846108 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Autophagy regulates selective HMGB1 release in tumor cells that are destined to die.

Cell death and differentiation ·Vol. 16 ·No. 1 ·2009-01-00 ·Pages 175-83

Thorburn J, Horita H, Redzic J, Hansen K, Frankel AE, Thorburn A

Abstract

Macroautophagy (hereafter referred to as autophagy) can increase or decrease the amount of cell death in response to various stimuli. To test whether autophagy also controls the characteristics associated with dying cells, we studied tumor cell killing by epidermal growth factor receptor-targeted diphtheria toxin (DT-EGF). DT-EGF kills epithelial and glioblastoma tumor cells with similar efficiency but by different mechanisms that depend on whether the cells activate autophagy when treated with the drug. Dying cells in which autophagy is induced selectively release the immune modulator high-mobility group B1 (HMGB1) without causing lysis of the cell membrane and classical necrosis. Conversely, cells that are killed by DT-EGF where autophagy is blocked, activate caspases but retain HMGB1. These data suggest that it may be feasible to manipulate the immunogenicity of dying cells by increasing or decreasing autophagy.

MeSH Terms
Autophagy/drug effects,immunology Cell Line, Tumor Diphtheria Toxin/pharmacology Epidermal Growth Factor/pharmacology Glioblastoma/immunology,metabolism HMGB1 Protein/immunology,metabolism Humans Immunologic Factors/immunology,metabolism Neoplasm Proteins/immunology,metabolism Neoplasms, Glandular and Epithelial/immunology,metabolism Recombinant Fusion Proteins/pharmacology
Chemicals
Diphtheria Toxin HMGB1 Protein Immunologic Factors Neoplasm Proteins Recombinant Fusion Proteins Epidermal Growth Factor
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Thorburn J
Department of Pharmacology, School of Medicine, University of Colorado Denver, Aurora, CO 80045, USA.
Horita H
Redzic J
Hansen K
Frankel A E
Thorburn A
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Article Info
Journal
Cell death and differentiation
Abbr.
Cell Death Differ
ISSN
1476-5403
DOI
10.1038/cdd.2008.143
Published
2009-01-00
Epub
2008-00-10
Pages
175-83
Language
English
Region
England
NLM ID
9437445
PMCID
PMC2605182
Subset
IM
Grants
NCI NIH HHS · CA111421 · United States
NCI NIH HHS · P30 CA046934 · United States
NCI NIH HHS · R01 CA111421-01 · United States
NCI NIH HHS · R01 CA111421 · United States
NCI NIH HHS · R01 CA111421-04 · United States
External Links
PubMed source DOI: 10.1038/cdd.2008.143 PMC Full Text View journal details
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