Scientists at Cardiff University have built an artificial blood vessel system that simulates the environment that cancer cells encounter in the body. The model has already been used to help understand the effectiveness of a new targeted drug for chronic lymphocytic leukaemia (CLL), one of the most common types of blood cancer.
The model accurately mimics capillary beds - the interweaving networks of capillaries where oxygen is transferred from the bloodstream to tissues and carbon dioxide is collected for return to the veins. Capillaries are the thinnest blood vessels in the body, with lining just one cell thick, also allowing for cells to migrate through the vessel walls.
CLL cells leave the circulatory system through these capillary beds and enter the bone marrow and lymph nodes where they can evade cancer treatment.
To create the model, which has been nicknamed ‘Maisy’, scientists introduced endothelial cells, which are the cells that naturally line the inner surface of blood vessels, into hollow fibres. When subjected to shear force by passing fluid through the fibre like blood through a vessel, the endothelial cells flatten against the fibre to form artificial capillaries. Leukaemia cells are then circulated through these vessels and their interactions with the endothelial cells studied.
The work, published in the journal Blood, was supported by Leukaemia & Lymphoma Research and the Leukaemia Research Appeal for Wales.
CLL cells that migrated out through the vessel walls had significantly higher levels of several molecules on their surface, the protein ‘CD49d’ in particular, compared with CLL cells that remained in circulation. The CD49d protein is thought to control cell migration. The observation that CLL cells that express CD49d are those that most readily ‘escape’ the blood stream provides some explanation for why patients with increased levels of this protein are known to have a poorer prognosis
Dr Elisabeth Walsby, who led the project at Cardiff University’s School of Medicine, said: “If leukaemia cells spread outside of the blood vessels into other parts of the body, it is much harder to kill them with traditional cancer drugs. This model has helped advance our understanding of the complex interactions between leukaemia cells and their microenvironments and the genes and proteins that govern this process.”
The researchers used the model to test a new antibody drug called Natalizumab, which can specifically seek out CD49d proteins on the surface of cells. When leukaemia cells in the model were treated with Natalizumab, there was significantly reduced migration out of the blood vessels, but it did not stop altogether. This suggests that either the inhibition of CD49d was not complete or that other characteristics of CLL cells enable them to migrate out of the vascular system.
Professor Chris Bunce, Research Director at Leukaemia & Lymphoma Research, said: “This innovative model provides important new opportunities for the study of new drugs that target molecules involved in cancer cell migration and homing. CLL is currently incurable - understanding gained from this research could have a profound impact of the design of treatments for the disease.”