Cell-surface expression of Hsp70 on hematopoietic cancer cells after inhibition of HDAC activity
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Cell-surface expression of Hsp70 on hematopoietic cancer cells after inhibition of HDAC activity. / Jensen, Helle; Andresen, Lars; Hansen, Karen Aagaard; Skov, Søren.
I: Journal of Leukocyte Biology, Bind 86, Nr. 4, 2009, s. 923-932.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Cell-surface expression of Hsp70 on hematopoietic cancer cells after inhibition of HDAC activity
AU - Jensen, Helle
AU - Andresen, Lars
AU - Hansen, Karen Aagaard
AU - Skov, Søren
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
U2 - 10.1189/jlb.0209056
DO - 10.1189/jlb.0209056
M3 - Journal article
C2 - 19502564
VL - 86
SP - 923
EP - 932
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
SN - 0741-5400
IS - 4
ER -
ID: 15430590