In a recent issue of the American Journal of Pathology, the Bremen researchers report their findings on a signalling molecule called "High Mobility Group Protein B1" (HMGB1). As a signal sent by tumour cells HMGB1 proteins induce sprouting of blood vessels that supply tumours with oxygen, thus promoting tumour growth.
Tumours cannot survive independently of their host's organism, where they grow like parasites. Akin to normal cells, tumour cells need an adequate supply of oxygen and nutrients for their survival and proliferation. Tumours usually do not exceed 1 - 2 mm in diameter in order to be adequately supplied by surrounding capillaries. Nevertheless, mechanisms exist allowing tumours to overcome these limitations: they send out angiogenetic signals, i.e. molecules that induce sprouting of new capillaries proximal to the tumour to provide it with oxygen and essential nutrients.
A particularly refined strategy used by tumours to overcome size limitation has now been discovered by a team of scientists headed by the human geneticist J?śrn Bullerdiek at the University of Bremen. The strategy starts with an area of the tumour that, due to a lack of oxygen, is characterized by the death of cells. HMGB1 is released from these necrotic cells and serves as a danger signal that calls capillaries to grow into the tumour. Thus, even dead cells of the tumour support its ability to grow.
HMGB1 is also now considered a target for therapeutic approaches aimed at reducing the vascular supply of tumours. Blocking of the angiogenetic signal, e.g. by antibodies, could reduce tumour cell growth and the spreading of tumours.
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Muller and Prendergast are enthusiastic about the new strategy for clinical treatment of other cancers in addition to breast cancer. "There is growing evidence that cancer cells elude detection by the immune system," Prendergast said. "Our findings suggest that by blocking IDO we can 'uncloak' cancer cells to the immune system in a way that will increase the efficiency of chemotherapeutic treatment(s)."
The Lankenau Institute for Medical Research is a hospital-based nonprofit research institute in suburban Philadelphia, PA. The Institute's mission is to improve human health and well being by uncovering causes and better treatments for cancer, heart disease, and other diseases of aging. A major focus of the Institute is to identify genetic risk factors for disease and to develop novel strategies for prevention and treatment of these diseases based on this information.
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