Thermally induced injury and heat-shock protein expression in cells and tissues. Ann N Y Acad Sci

Department of Biomedical Engineering, University of Texas at Austin, Austin, Texas, United States
Annals of the New York Academy of Sciences (Impact Factor: 4.38). 01/2006; 1066(1):222-42. DOI: 10.1196/annals.1363.009
Source: PubMed


Heat-shock proteins (HSPs) are critical components of a cell's defense mechanism against injury associated with adverse stresses. Initiating insults, such as elevated or depressed temperature, diminished oxygen, and pressure, increase HSP expression and can protect cells against subsequent, otherwise lethal, insults. Although HSPs are very beneficial to the normal cell, cancer cells can also use HSPs in response to stresses associated with various therapies (hyperthermia, chemotherapy, radiation), mitigating injury incurred by these treatments. Hyperthermia is a common treatment option for prostate cancer. HSPs can be induced in regions of the tumor where temperatures are insufficient to cause lethal thermal necrosis. Elevated HSP expression can enhance tumor cell viability and impart increased resistance to subsequent chemotherapy and radiation treatments, thereby promoting tumor recurrence. An understanding of the structure, function, and thermally stimulated HSP kinetics and cell injury for prostate cancer cells is essential to designing effective hyperthermia protocols. Measured thermally induced cellular HSP expression and injury data can be employed to develop a treatment planning model for optimization of the tissue response to therapy based on accurate prediction of the HSP expression and cell damage distribution.

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Available from: Yusheng Feng, Oct 28, 2014
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    • "When exposed to elevated temperatures, animal cells synthesize a small number of highly conserved proteins called heat-shock proteins (Hsps) (Lindquist 1986). Induction of Hsp expression has been reported to protect cells against subsequent temperature changes as well as diminished oxygen and pressure, and loss of Hsp expression may cause damage or be lethal (Marber et al. 1995; Ryan et al. 1992; Rylander et al. 2005; Villar et al. 1994; Wischmeyer 2002). For example, suppressed Hsp90 and Hsp27 expression resulted in increased endoplasmic reticulum stress (ER stress) and apoptosis (Lamoureux et al. 2013). "
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    ABSTRACT: We investigated whether acetyl salicylic acid (ASA) protects chicken myocardial cells from heat stress-mediated damage in vivo and whether the induction of Hsp27 expression is connected with this function. Pathological changes, damage-related enzyme levels, and Hsp27 expression were studied in chickens following heat stress (40 ± 1 °C for 0, 1, 2, 3, 5, 7, 10, 15, or 24 h, respectively) with or without ASA administration (1 mg/kg BW, 2 h prior). Appearance of pathological lesions such as degenerations and karyopyknosis as well as the myocardial damage-related enzyme activation indicated that heat stress causes considerable injury to the myocardial cells in vivo. Myocardial cell injury was most serious in chickens exposed to heat stress without prior ASA administration; meanwhile, ASA pretreatment acted protective function against high temperature-induced injury. Hsp27 expression was induced under all experimental conditions but was one-fold higher in the ASA-pretreated animals (0.3138 ± 0.0340 ng/mL) than in untreated animals (0.1437 ± 0.0476 ng/mL) 1 h after heat stress exposure, and such an increase was sustained over the length of the experiment. Our findings indicate that pretreatment with ASA protects chicken myocardial cells from acute heat stress in vivo with almost no obvious side effects, and this protection may involve an enhancement of Hsp27 expression. However, the detailed mechanisms underlying this effect require further investigation.
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    • "HSPs are up-regulated in tumor cells and their protective effects confound thermal therapies, thus their expression should be controlled in order to achieve an optimal thermal therapy [29]. Laser treatments such as hyperthermia can be optimized by setting the optimum laser parameters (wavelength, power, pulse duration and delivery method) to satisfy the prescribed HSP expression distributions in tumor and healthy tissue required to minimize injury to healthy tissue and efficient tumor destruction [30]. "
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    ABSTRACT: In order to develop effective laser-based therapeutics, the extent of laser-induced damage must be quantified for given laser parameters. Therefore, we want to determine the spatiotemporal expression patterns of heat shock proteins, both to understand the roles of heat shock proteins in laser-induced tissue damage and repair and to develop heat shock proteins as tools to illustrate the extent of laser-induced damage and wound healing following irradiation. We exposed anesthetized mice to the focused beam of a short-pulse Nd:YAG laser (1064nm; 200ns pulsewidth) for 15s, while measuring temperature distribution in the skin using an infrared thermal camera. Following irradiation, we examined expression of HSP47 and HSP70 over time (0-24h) as indicators of the heat shock response and recovery from damage in the laser-irradiated region. Expression patterns of HSP70 and HSP47 as detected by immunohistochemistry and confocal microscopy delineate the extent of damage and the process of healing in tissue. Both HSP70 and HSP47 were expressed in dermis and epidermis following laser irradiation, and the spatial and temporal changes in HSP expression patterns define the laser-induced thermal damage zone and the process of healing in tissues. HSP70 may define biochemically the thermal damage zone in which cells are targeted for destruction, and HSP47 may illustrate the process of recovery from thermally induced damage. Studying the effects of different laser parameters on the expression of HSPs will allow development of effective laser therapies that provide accurate and precise tissue ablation and may promote rapid wound healing following laser-based surgery.
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    • "Activation of proteotoxic stress pathways such as the HSR have been proposed to not only support tumour cell survival following a variety of insults but may also be a major factor in promoting tumour progression (Dai et al. 2007; Rylander et al. 2005). Activation of the transcription factor, HSF1, is synonymous with HSR induction; however, in addition to its ability to confer enhanced survival of cells, HSF1 can also regulate many other cellular processes. "
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    ABSTRACT: Current cancer therapies including cytotoxic chemotherapy, radiation and hyperthermic therapy induce acute proteotoxic stress in tumour cells. A major challenge to cancer therapeutic efficacy is the recurrence of therapy-resistant tumours and how to overcome their emergence. The current study examines the concept that tumour cell exposure to acute proteotoxic stress results in the acquisition of a more advanced and aggressive cancer cell phenotype. Specifically, we determined whether heat stress resulted in an epithelial-to-mesenchymal transition (EMT) and/or the enhancement of cell migration, components of an advanced and therapeutically resistant cancer phenotype. We identified that heat stress enhanced cell migration in both the lung A549, and breast MDA-MB-468 human adenocarcinoma cell lines, with A549 cells also undergoing a partial EMT. Moreover, in an in vivo model of thermally ablated liver metastases of the mouse colorectal MoCR cell line, immunohistological analysis of classical EMT markers demonstrated a shift to a more mesenchymal phenotype in the surviving tumour fraction, further demonstrating that thermal stress can induce epithelial plasticity. To identify a mechanism by which thermal stress modulates epithelial plasticity, we examined whether the major transcriptional regulator of the heat shock response, heat shock factor 1 (HSF1), was a required component. Knockdown of HSF1 in the A549 model did not prevent the associated morphological changes or enhanced migratory profile of heat stressed cells. Therefore, this study provides evidence that heat stress significantly impacts upon cancer cell epithelial plasticity and the migratory phenotype independent of HSF1. These findings further our understanding of novel biological downstream effects of heat stress and their potential independence from the classical heat shock pathway.
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