Endothelial cells and hyperthermia.

Most radiation oncologists are aware of the effects of clinical hyperthermia on neoplastic cells. Its effects on blood vessels, however, are not as well recognized. Yet, since the 1960s a number of investigators have described and categorized the effects of hyperthermia on microvessels (in vivo), and on cultured endothelial cells (EC) (in vitro). Both EC and microvessels can be lethally damaged by the hyperthermia doses used as antineoplastic therapy. In vitro data indicate that capillary EC are moderately sensitive to hyperthermia. Proliferating EC are more thermosensitive suggesting that microvessels of malignant neoplasms (which contain many proliferating EC) are more affected than microvessels of normal tissues. This differential sensitivity of microvessels has also been observed in blood flow studies. Furthermore, hyperthermia inhibits angiogenesis. Thus, some of the antineoplastic effects of heat are caused by ischaemia due to obstruction or destruction of the tumour vessels or to inability to form new vessels. Sublethal EC damage can also be demonstrated, resulting in decreased synthesis of most proteins including adhesion molecules (as well as increased expression of a few such as heat shock proteins) and producing reversible loss of cytoskeletal elements. The therapeutic advantage provided by the higher thermal sensitivity of neoplastic vessels should be exploited further, perhaps by developing strategies specifically aimed to the tumour microvasculature.