A team of cancer researchers from Australia and the UK have bred a biosensor mouse that has enabled them to watch as pancreatic cancer cells ‘unzip’ right before they begin to spread.
“Our biosensor mouse makes it possible to look at a primary tumour that has not yet spread: in real time, in 3D, and in a living tumour. Using state-of-the-art laser technology, we can see, at a molecular level, whether the contacts that hold tumour cells in place have started to unzip – and that’s a sign that the cancer is about to spread,” says Dr Paul Timpson of Sydney’s Garvan Institute of Medical Research.
To understand how unzipping contributes to the spread of pancreatic cancer, the researchers implanted a genetic model of invasive pancreatic cancer. Remarkably, the researchers were able to successfully rezip these cancer cells by treating them with anti-cancer therapies, stopping the spread of cancer before it had begun.
To make the biosensor, the researchers bred a mouse in which a key “zippering” protein that holds cells together – called E-cadherin – was linked to a protein from jellyfish that glows green in fluorescence microscopy. This allowed for them to pinpoint when key changes occured.
Which is incredibly important given that five-year pancreatic cancer survival rates stand at just 6.1% – a figure that has barely changed in the last 40 years. “Many patients present with pancreatic cancer at a very advanced stage, when the cancer has already spread to other tissues such as the liver,” says Dr Timpson.
“But sometimes, the cancer is detected before it has spread – and that’s the point where we have an opportunity to intervene and stop it in its tracks. If we give a drug early enough, we can rezip those cells together.”
Dr Timpson says the most exciting part of the study was the fact that the existing treatment – an anti-invasive drug called dasatinib – allowed us to stabalise the primary tumour. “We treated mice that had developed pancreatic cancer that had yet to spread with the anti-invasive drug [and] within three days of treatment, we saw cells within the tumour had re-zippered, and the tumour had stabilised.”
Similar results were achieved with a second therapy, saracatinib.
“The biosensor mouse is a powerful tool for anti-cancer drug discovery,” Dr Timpson says. “It makes it possible to evaluate the effect of new therapies on tumour spread, in real time and in a system that reflects human cancer as closely as is currently possible.”
Dr Timpson points out that this is just the beginning for the biosensor mouse. “We now have a model that is one step ahead of the invasion process in pancreatic cancer – but we are also already using this model in our laboratory for other aggressive and highly invasive cancer types, such as breast cancer.
“Ultimately, we expect to use the biosensor mouse to explore zippering and cancer spread in a wide range of tumours throughout the body.”
The Garvan Institute of Medical Research has received three ACRF cancer research grants totalling $6.13m. To read the original article, click here.