08:43am Sunday 24 September 2017

Blood EPO protein important in cancer development and spread

The findings are published in the journal Nature Medicine.

Yihai Cao Photo: John Sennett

Angiogenesis is the formation of new blood vessels based on the older vessels. The process is one of the most important areas of research for treating such diverse conditions as cancer, metastases, obesity, heart disease, stroke, diabetes and chronic inflammation. Even in healthy individuals is angiogenesis important and involved inter alia in wound healing and the menstrual cycle. Professor Yihai Cao and his research group at Karolinska Institutet studying angiogenesis and its link to cancer, and in the study now published in Nature Medicine shows the importance of a growth factor, PDGF-BB.

– It is a member of the PDGF family, which originates from the platelets in the blood and regulating cell growth and regulation. It also plays an important role in the development of blood vessels and contribute to uncontrolled blood vessel development that is a hallmark of cancer. Our preclinical findings suggest that PDGF-BB cause systemic effects in people with cancer, that is, it seems not only locally, but it goes into the blood and affects multiple organ dysfunction so that the whole body is affected, says Yihai Cao.

The studies were conducted in mice and may in the study show that when the growth factor PDGF-BB binds its receptor stimulates blood protein EPO (erythropoietin), which in turn controls the production of red blood cells and it may be the tumor to grow – the more cells that are the more oxygen to the tumors and then get promoted tumor growth.

– EPO has several functions: it produces more blood and stimulates angiogenesis. We show the mechanisms behind, and a nearby stimulation of tumor angiogenesis by directly receive endothelial cells to proliferate, the ability to move, grow and form the so-called tubular, and the fact that PDGF-BB promotes stimulation of extramedullary haematopoiesis – enlargement of the liver and spleen – which leads to increased syreperfusion and protection from anemia, says Yihai Cao.

Introduction of PDGF-BB in mice thus increases erythropoietin production and hematopoietic parameters.

– We believe that the increase of EPO may be responsible for tumor resistance to anti-angiogenesis therapy, which just goes to PDGF. By combining drugs targeting both PDGF and EPO could provide therapeutic benefits and may have to bypass the currently major resistance problems, says Yihai Cao, adding that they will now continue to study mouse models, as well as looking at opportunities for further clinical studies on patients.

Professor Yihai Cao is also affiliated with the University of Linköping. In the study were researchers from the Karolinska Institute, Linköping University and the University of Toyama, Japan participated.

Publication:

Yuan Xue, Sharon Lim, Yunlong Yang, Zongwei Wang, Lasse Dahl Ejby Jensen, Eva Maria Hedlund, Patrik Andersson, Masakiyo Sasa Hara, Ola Larsson, Dagmar Galten, Renhai Cao, Kayoko Hosaka & Yihai Cao

PDGF-BB modulator hematopoiesis and tumor angiogenesis by inducing erythropoietin production in stromal cells

Nature Medicine AOP 4 December 2011

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