Measurement and mathematical modeling of thermally induced injury and heat shock protein expression kinetics in normal and cancerous prostate cells.
OBJECTIVE
Hyperthermia can induce heat shock protein (HSP) expression in tumours, which will cause enhanced tumour viability and increased resistance to additional thermal, chemotherapy, and radiation treatments. The study objective was to determine the relationship of hyperthermia protocols with HSP expression kinetics and cell death and develop corresponding computational predictive models of normal and cancerous prostate cell response.


METHODS
HSP expression kinetics and cell viability were measured in PC3 prostate cancer and RWPE-1 normal prostate cells subjected to hyperthermia protocols of 44° to 60°C for 1 to 30 min. Hsp27, Hsp60, and Hsp70 expression kinetics were determined by western blotting and visualised with immunofluorescence and confocal microscopy. Based on measured HSP expression data, a mathematical model was developed for predicting thermally induced HSP expression. Cell viability was measured with propidium iodide staining and flow cytometry to quantify the injury parameters necessary for predicting cell death following hyperthermia.


RESULTS
Significant Hsp27 and Hsp70 levels were induced in both cell types with maximum HSP expression occurring at 16 h post-heating, and diminishing substantially after 72 h. PC3 cells were slightly more sensitive to thermal stress than RWPE-1 cells. Arrhenius analysis of injury data suggested a transition between injury mechanisms at 54°C. HSP expression and injury models were effective at predicting cellular response to hyperthermia.


CONCLUSIONS
Measurement of thermally induced HSP expression kinetics and cell viability associated with hyperthermia enabled development of thermal dosimetry guidelines and predictive models for HSP expression and cell injury as a function of thermal stress to investigate and design more effective hyperthermia therapies.
Rylander
Marissa Nichole
MN
School of Biomedical Engineering and Sciences and Department of Mechanical Engineering, Virginia Tech, Blacksburg, Virginia 24060, USA. mnr@vt.edu
Feng
Yusheng
Y
Zimmermann
Kristen
K
Diller
Kenneth R
KR
D045744:Cell Line, Tumor; D002470:Cell Survival; D018834:Chaperonin 60 / Q000378:metabolism*; D005334:Fever / Q000473:pathology*; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D008962:Models, Theoretical; D011467:Prostate / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy
D018834:Chaperonin 60; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins