Medical theory overturned

New research conducted by a group of EU-funded researchers is shedding new light on the way blood vessels grow, overturning years of medical thought, the findings have important implications
for the development of novel drugs to treat diseases such as cancer, many of which target the tumour’s ability to grow its own blood vessels.

Angiogenesis is the process of growing new blood vessels. It is a normal process in growth and development, and plays a key role in a number of diverse situations including healing wounds and
traumas, cardiovascular disorders, inflammatory conditions such as rheumatoid arthritis, and in cancer growth. However, it is also a fundamental step in the transition of tumours from a dormant
state to a malignant state.

Current thinking holds that the endothelial cells which line the blood vessel wall have their origins in circulating stem cells which are first mobilised from the bone marrow. These
subsequently differentiate to produce mature bona fide endothelial cells which are incorporated into the blood vessels. This concept has become textbook material, and a common theme in modem
vascular and cancer biology. Crucially, it was also believed that cancerous tumours also relied on these circulating stem cells to build up their own networks of blood vessels.

However, new research coming out of Europe and the US shows that bone marrow-derived circulating endothelial precursors do not contribute to the vascular endothelium, and they are not needed
for tumour growth either. The research was led by Dr Petri Salvén from the University of Helsinki, Finland, and stem cell research pioneer Dr Irving Weissman at Stanford University,

Together they succeeded in showing that circulating endothelial precursor cells do not actually exist and that angiogenesis and cancer growth neither involve nor depend on such hypothetical
stem cells. They were able to show this by studying angiogenesis in mice using the latest in three dimensional cellular imaging technologies.

The researchers note that both blood vessels and tumour tissues contain large numbers of bone marrow derived cells such as ordinary white blood cells that are often very close to blood vessel
walls. They speculate that these may have been misinterpreted as blood vessel wall endothelial cells in earlier studies using less advanced technologies.

The results have great practical significance for researchers who are trying to develop novel cancer treatments designed to target the normal cells of the body which supply tumours with blood
and nutrients. ‘Our results will help the researchers to concentrate their efforts on molecular and cellular targets that actually exist,’ says Dr Salvén, leader of the Helsinki team.

‘It has been a learning experience to try to publish results that demonstrate that a number of fellow researchers have for years been studying nonexistent cells,’ Dr. Salvén comments.
‘Issues concerning publication bias and non-accessibility of negative data are really becoming more and more relevant, just as recently seen also in other fields of biomedicine.’

Their findings are to be published in the journal of the Proceedings of the National Academy of Sciences of the United States of America. EU support for the work came from the EU-funded
‘Tumor-Host Genomics’ project, which is financed through the ‘Life sciences, genomics and biotechnology for health’ Thematic Area of the Sixth Framework Programme (FP6).

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