Cell-surface expression of Hsp70 on hematopoietic cancer cells after inhibition of HDAC activity.
We show that inhibition of HDAC activity leads to surface expression of Hsp70 on various hematopoietic cancer cells, an occurance that was not observed on naïve or activated peripheral blood cells. HDAC inhibitor-mediated Hsp70 surface expression was confined to the apoptotic Annexin V-positive cells and blocked by inhibition of apoptosis. Other chemotherapeutic inducers of apoptosis such as etoposide and camptothecin also led to a robust induction of Hsp70 surface expression. Hsp70 expression was, however, not caused by induction of apoptosis per se, as activated CD4 T cells remained Hsp70 surface-negative despite effective induction of apoptosis. Interestingly, inhibition of endolysosomes or normal ER/Golgi transport did not affect Hsp70 surface expression. Intracellular calcium and the transcription factor Sp1, which has been shown previously to be important for the intracellular stress mediated by HDAC inhibitors, were not involved in Hsp70 surface expression. We also found that HDAC inhibitors decreased cellular PMET activity and that a selective inhibition of PMET activity with extracellular NADH induced a robust Hsp70 surface expression. Our data suggest that inhibition of HDAC activity selectively induces surface expression of Hsp70 on hematopoietic cancer cells and that this may increase immunorecognition of these cells.
Jensen
Helle
H
Laboratory of Immunology, Faculty of Life Sciences, University of Copenhagen, 1870 Frederiksberg C, Denmark.
Andresen
Lars
L
Hansen
Karen Aagaard
KA
Skov
Søren
S
D017304:Annexin A5 / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D002166:Camptothecin / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005047:Etoposide / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis*; D006412:Hematopoietic Stem Cells / Q000378:metabolism* / Q000473:pathology; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D020014:K562 Cells; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D016329:Sp1 Transcription Factor / Q000378:metabolism
D017304:Annexin A5; D000972:Antineoplastic Agents, Phytogenic; D004791:Enzyme Inhibitors; D018840:HSP70 Heat-Shock Proteins; D056572:Histone Deacetylase Inhibitors; D009363:Neoplasm Proteins; D016329:Sp1 Transcription Factor; D005047:Etoposide; D006655:Histone Deacetylases; D002166:Camptothecin