Differential heat shock protein localization in chronic lymphocytic leukemia.
Mechanisms behind carcinogenesis and resistance of tumor cells to treatment regimes remain elusive. The major stress proteins Hsp72, Hsp90, and Hsp27 are credible candidates to provide this resistance, as their overexpression in many cancer types is well documented. In addition to being present inside tumor cells, where they confer resistance to apoptosis, Hsp72, in particular, is presented externally, embedded in the cell membrane of cancer cells. This study aimed to investigate the localization of Hsp72, Hsp90, and Hsp27 in leukocytes from patients with CLL and age-matched control subjects. CLL patients were found to express significantly higher levels of iHsp90 (CLL=2463 MFI; control=748 MFI) and iHsp27 (CLL=2190 MFI; control=1031 MFI) in lymphocytes than that expressed by lymphocytes from control subjects. Furthermore, expression of iHsp90 was shown to be related to stage of disease, and expression of iHsp27 correlated with levels of active caspase-3. Patients were found to express very high levels or very low levels of sHsp72 and iHsp72 in CD5(+)/CD19(+) cells, although surface and intracellular datasets did not correlate. Levels of extracellular Hsp72 circulating in the serum were found to correlate with internal levels of Hsp72 and were also found to be significantly lower in patients receiving corticosteroid treatment than in patients not receiving corticosteroid treatment. Finally, analysis of the number of circulating Tregs revealed significantly elevated numbers in CLL patients compared with control subjects.
Dempsey
Nina C
NC
Chester Centre for Stress Research, University of Chester, Chester, United Kingdom.
Leoni
Francesca
F
Ireland
H Elyse
HE
Hoyle
Christine
C
Williams
John H H
JH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018941:Antigens, CD19 / Q000378:metabolism; D018791:CD4 Lymphocyte Count; D018956:CD5 Antigens / Q000378:metabolism; D016022:Case-Control Studies; D053148:Caspase 3 / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D018450:Disease Progression; D004789:Enzyme Activation; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism; D050884:HSP72 Heat-Shock Proteins / Q000097:blood / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D021381:Protein Transport; D050378:T-Lymphocytes, Regulatory / Q000201:enzymology / Q000473:pathology
D018941:Antigens, CD19; D018956:CD5 Antigens; D055551:HSP27 Heat-Shock Proteins; D050884:HSP72 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D053148:Caspase 3