Inhibition of Epithelial-to-Mesenchymal Transition (EMT) by Hyperthermia

Abstract

Hyperthermia therapy suppresses tumor growth through deliberate heating. To further enhance the antitumor effect, it is often combined with radiation or chemotherapy. In addition, hyperthermia may reduce the metastatic potential of cancer cells and inhibit tumor metastasis. However, the underlying mechanisms through which hyperthermia inhibits cancer metastasis have yet to be fully elucidated. Epithelial-to-mesenchymal transition (EMT) plays a key role in tumor metastasis; therefore, the aim of this chapter is to summarize the effects and underlying mechanisms of EMT in cancer cells. The results suggest that hyperthermia not only inhibits tumor growth, but also mediates the expression of EMT-related genes-including E-cadherin and vimentin-and a number of transcription factors important for cancer cell motility, invasiveness, and metastasis during tumorigenesis. Furthermore, hyperthermia may also reverse alterations in cell morphology induced by transforming growth factor-β (TGF-β) and/or hypoxia, as well as the increased cell invasiveness characteristic of EMT. Taken together, these data indicate that hyperthermia suppresses cancer migration and invasion through the inhibition of EMT. Keywords EMT • E-cadherin • Vimentin • TGF-β Hyperthermia and MetastasesHyperthermia is a therapeutic method that suppresses tumor growth through the deliberate heating of a primary tumor. The antitumor effect of hyperthermia is enhanced when used in combination with radiation or chemotherapy. Moreover, a previous study in an animal model demonstrated that local hyperthermia can inhibit tumor metastasis [1], and a clinical trial demonstrated that local hyperthermia could be effective for treating cervical lymph node metastasis in oral cancer [2]. In addition, in our previous study, we reported the potential of hyperthermia for