Researchers model embryo implantation and tumour metastasis in f...( vation and the Ontario Innovation Trust...)

vation and the Ontario Innovation Trust. Looking for a marker that would enable him to see live cells - particularly those of the extraembryonic tissues - as they change their shape and motion, Dr. Reed saw the molecules that he would eventually identify as basigin. The molecules were attached to the membrane of the yolk sac, a placenta-like structure that feeds the fruit fly embryo.

When integrin and basigin molecules were depleted, the extraembryonic membranes could not establish close contacts, equivalent to mammalian embryos not implanting. In addition, Dr. Reed found that membrane contact was required for survival of the tissues. In mutants, the tissues fall apart and die. This has an exciting connection to tumour cell metastasis in humans. "When a tumour metastasizes, cells in fact have to decide to leave it and invade other tissues," said Dr. Reed. "Here, in flies, you have cells leaving the tissue, but their fate is instead, to die. All you need is something that prevents cells from dying when they leave the tissue and they would immediately become 'immortal' and invasive."

"If you think about how the placenta has to be formed it is an invasive process and must be regulated so that it doesn't behave like a metastatic tumour," said Dr. Reed. "The implication is that there is a fine balance between the good kind of invasion and the bad kind."

In mammals, basigin is expressed on the surface of 60 per cent of human gliomas, a type of nervous system tumour, and prior research has shown that the higher the level of expression of basigin the more invasive the tumour. Eventually, the research team may be able to model the molecular basis of metastasis using flies. The next steps involve the detailed study of the molecular biology of the tissue contact process and the 'metastatic' behaviour of the cells as they leave the tissue in mutants.

Other members of the research team included Dr. Ronit Wilk of The Hospital for Sick Children
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Contact: Chelsea Gay
chelsea.gay@sickkids.ca
416-813-7654 x1042
University of Toronto
11-Mar-2004

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