Tumour blood supply stopped in its tracks by dextran-catechin
August 9, 2017
Researchers have discovered how a modified natural compound disrupts angiogenesis, the formation of blood vessel networks, in neuroblastoma tumours, stopping them laying down the vital supply lines that fuel cancer growth and spread.
The international study, led by scientists at Children’s Cancer Institute and UNSW, is published in the journal Scientific Reports and paves the way for less toxic treatments for neuroblastoma, a childhood cancer with an average age of diagnosis of just one to two years old.
Lead author Dr Orazio Vittorio of Children’s Cancer Institute found in 2012 that the natural polyphenol catechin slows tumour growth in the laboratory but breaks down too quickly in the body to be effective.
“We joined catechin with a sugar called dextran. We found this dextran-catechin complex is much more stable in the body and that it slows tumour growth by affecting copper levels – but we didn’t know precisely how,” he said.
The new research showed that copper is needed by endothelial cells, the cells that line blood vessels, and that dextran-catechin disrupts the cells’ copper levels in several ways.
“Dextran-catechin inhibits specific copper transport proteins in the cells that line the blood vessels, altering intracellular copper levels. This prevents the cells joining together to form the network of vessels that supplies tumours with blood to keep growing” he said.
The result is clearly visible down a microscope. When human endothelial cells were cultured and treated with dextran-catechin, the normally branching networks of blood vessels failed to form properly. Likewise, in mice, neuroblastoma tumours treated with dextran-catechin had significantly fewer blood vessels than tumours treated with saline control.
“Instead of forming a neat, branching network of blood vessels, you see a mess of cells all over the place, which means cancer cells can’t get the blood supply they need,” explained Dr Vittorio.
“This is exciting because it’s a new target for the childhood cancer neuroblastoma that appears safe and has minimal side effects”, he said.
Copper is needed to switch on genes that help endothelial cells grow and form blood vessels during angiogenesis. The study found that dextran-catechin targets specific proteins that control copper uptake and removal in endothelial cells, reducing the copper available to switch on the genes.
Further laboratory research into dextran-catechin’s potential as a future treatment is underway.
Researchers include Mr Eugene Yee from UNSW Science, Dr Orazio Vittorio and other researchers from Children’s Cancer Institute and the Australian Centre for NanoMedicine led by Professor Maria Kavallaris, ARC Centre of Excellence in Bio-Nano Science and Technology, and overseas researchers from universities in France and Italy.
Dr Vittorio presented the findings at the Nanotech France 2017 conference in Paris on 29 June.
Read the paper in Scientific Reports ‘Dextran-Catechin inhibits angiogenesis by disrupting copper homeostasis in endothelial cells’ by Eugene M. H. Yee, Miriam B. Brandl, Eddy Pasquier, Giuseppe Cirill, Kathleen Kimpton, Maria Kavallaris, Naresh Kumar, Orazio Vittorio
Images of untreated cells (see main image) and dextran-catechin treated cells are available on request.
About Children’s Cancer Institute
Originally founded by two fathers of children with cancer in 1976, Children’s Cancer Institute is the only independent medical research institute in Australia wholly dedicated to research into the causes, prevention and cure of childhood cancer. Forty years on, our vision remains unchanged – to save the lives of all children with cancer and to eliminate their suffering. The Institute has grown to now employ more than 220 researchers, operational staff and students, and has established a national and international reputation for scientific excellence.
Our focus is on translational research, and we have an integrated team of laboratory researchers and clinician scientists who work together in partnership to discover new treatments which can be progressed from the lab bench to the beds of children on wards in our hospitals as quickly as possible. These new treatments are specifically targeting childhood cancers, so we can develop safer and more effective drugs and drug combinations that will minimise side-effects and ultimately give children with cancer the best chance of a cure with the highest possible quality of life.
We are currently leading the establishment of the Zero Childhood Cancer national child cancer personalised medicine program for children with the most aggressive cancers, in partnership with the Sydney Children’s Hospitals Network. This program will revolutionise the way treatment decisions are made, with the aim of improving survivorship for those children at highest risk of treatment failure from their disease.