New possibilities impede tumour growth
The formation of new blood vessels is necessary for a cancer tumour to grow. Stopping this process is therefore an important goal in cancer research. Researchers at Karolinska Institutet (KTH), Linköping University (LiU), and University of Toyama in Japan have now charted the mechanism that stimulates vessel formation. The result, published in Nature Medicine, opens up new possibilities for treatment.
Researchers can show the importance of a growth hormone, PDGF-BB, and the blood protein EPO for the rise of cancer and the spread of tumours in the body. In the future, the discovery will provide new opportunities to attack tumour growth and circumvent the problems associated with resistance many of today’s medicines are subject to.
Angiogenesis is the formation of new capillaries starting from existing blood vessels. The process is one of the most important goals for treating different conditions such as cancer, obesity, cardiac disease, stroke, diabetes, and chronic inflammation. Even in healthy individuals, angiogenesis is important when healing injuries and even the menstrual cycle. Professor Yiai Cao (pictured) and his research group are studying angiogenesis and its links to cancer, and in the newly published study they demonstrate the importance of a growth factor, PDGF-BB.
“It’s a member of the PDGF family, which originates in the blood platelets and which regulate the growth and control of the cell. It also plays an important role in the development of blood vessels, and contributes to uncontrolled blood vessel growth, which is a hallmark of cancer. Our preclinical discoveries indicate that PDGF-BB causes systemic effects in people with cancer – that is, it doesn’t only operate locally, but also enters the bloodstream and affects the functions of several organs,” Cao says.
Studies carried out on mice show that when PDGF-BB binds to its receptor, the blood protein erythropoietin (EPO) is stimulated, which in turn controls the production of red blood cells. The more blood cells that are formed, the more oxygen the tumour gets, which, in turn, favours growth.
The researchers show on the one hand how EPO directly causes endothelial cells to increase, move, sprout and form tubes, and on the other that PDGF-BB promotes the stimulation of what is called extramedullary hematopoiesis, which leads to increased oxygen transport and protects the tumour against shortages of blood.
The hope is that a combination of medicine targeting PDGF and EPO should be able to provide more effective treatment and overcome the tumour’s resistance against anti-angiogenesis treatment.
Cao also works as a guest professor at the at LiU, where co-author Lasse D. Jensen will be admitted as a postdoc in December. Here, research is focused on the significance of angiogenesis in cardiovascular disease, with zebra fish as the modelling system.
Photo: John Sennet
Article: PDGF-BB modulates hematopoiesis and tumor angiogenesis by inducing erythropoietin production in stromal cells by Yuan Xue, Sharon Lim, Yunlong Yang, Zongwei Wang, Lasse Dahl Ejby Jensen, Eva–Maria Hedlund, Patrik Andersson, Masakiyo Sasahara, Ola Larsson, Dagmar Galter, Renhai Cao, Kayoko Hosaka and Yihai Cao, Nature Medicine AOP 4 December 2011.
Last updated: 2012-12-10