Heat shock proteins, thermotolerance, and their relevance to clinical hyperthermia

Mammalian cells, when exposed to a non-lethal heat shock, have the ability to acquire a transient resistance to subsequent exposures at elevated temperatures, a phenomenon termed thermotolerance. The mechanism(s) for the development of thermotolerance is not well understood, but earlier experimental evidence suggests that protein synthesis may play a role in its manifestation. On the molecular level, heat shock activates a specific set of genes, so-called heat shock genes, and results in the preferential synthesis of heat shock proteins. The heat shock response, specifically the regulation, expression and functions of heat shock proteins, has been extensively studied in the past decades and has attracted the attention of a wide spectrum of investigators ranging from molecular and cell biologists to radiation and hyperthermia oncologists. There is much data supporting the hypothesis that heat shock proteins play important roles in modulating cellular responses to heat shock, and are involved in the development of thermotolerance. This review summarizes some current knowledge on thermotolerance and the functions of heat shock proteins, especially hsp70. The relationship between thermotolerance development and hsp70 synthesis in tumours and in normal tissues is examined. The possibility of using hsp70 as an indicator for thermotolerance is discussed.