Phosphoryated HSP90-alpha expression in peripheral blood leukocytes from cisplatin-treated cancer patients

SOTTILE FLEURY ML; GARCÍA MB; VARGAS ROIG LM; GOMEZ LC; GONZALEZ L; NADIN SB; REDONDO AL; IBARRA J

Congreso; Reunión de Sociedades de Biociencias: LX Reunión Científica de la Sociedad Argentina de Investigación Clínica, LXVIII Reunión Anual de la Sociedad Argentina de Inmunología (SAI), Reunión Anual de la Sociedad Argentina de Fisiología (SAFIS); 2020

The heat shock protein HSP90 plays important roles in protein homeostasis. The inducible form, HSP90α, may be an attractive target for new anticancer therapies, as many of its client proteins are involved in cancer hallmarks. The phosphorylated form in Thr-7 (p-HSP90α) accumulates at the DNA damage sites and has been proposed as a biomarker of genomic instability. Cisplatin (cisPt) is used for the treatment of solid tumors, but resistance limits its efficacy. Therefore, it is important to identify biomarkers to predict treatment response. Our aim was to evaluate the predictive/prognostic value of p-HSP90α in peripheral blood leukocytes (PBL) from cisPt-treated cancer patients. PBL from 7 healthy persons and 52 patients before chemotherapy were in vitro exposed to cisPt (200 µM, 1 h). The cells were harvested at: T0 (immediately after cisPt), at T24 and at T48 (after a recovery period of 24h and 48h, respectively). Nuclear and cytoplasmic expression of p-HSP90α was evaluated by immunocytochemistry. At basal conditions, cytoplasmic and nuclear p-HSP90α did not show statistically significant differences between healthy individuals and cancer patients. After cPt-treatment, the cytoplasmic levels of the protein did not significantly differ between experimental conditions, in both controls and patients. In contrast, the nuclear expression of p-HSP90α significantly increased in patients at T24 (P