• Fluorescent E-cadherin zippering protein (green), holding tumour cells together, preventing their spread in surrounding collagen tissue (purple). (Garvan Institute)
New biosensor mouse helps researchers stop cancer in its tracks before it spreads to other organs.
By
Signe Dean

6 Jan 2016 - 9:41 AM  UPDATED 15 Feb 2016 - 5:03 PM

A large team of scientists from Australia and the UK have created a “biosensor mouse” in which they can track pancreatic cancer cells in real time with the help of fluorescence.

Using this new biosensor technique, the researchers even managed to prevent aggressive pancreatic cancer cells from spreading in a live mouse. In time, this biosensor tool could lead to better testing of new, promising cancer drugs.

“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,“ said Dr Paul Timpson from Sydney’s Garvan Institute of Medical Research, who co-led the study with Prof Kurt Anderson of the Beatson Institute for Cancer Research (UK).

To create the biosensor mouse, researchers attached a green fluorescent protein from jellyfish to a molecule called E-cadherin - a protein involved in holding cells together. When this molecule stops working properly, cancer cells can become invasive.

“In pancreatic cancer, before it spreads, this molecule must “unzip”, the cells must stop touching each other so they’re not held together, and then they start invading the body,” said Timpson. Once these tumour cells settle in other organs, it becomes a metastasis - and most types of metastatic cancer currently can’t be treated.

Once the protein “zipper” molecule was made glow-in-the-dark, researchers could use a laser to determine how tightly the cells were holding together. They could watch in real time as the tumour cells started to lose the protein zipper holding them in place - catching the moment before cancer would set off on an invasive spread.

 

Stopping the cancer in its tracks

Pancreatic cancer doesn’t have a routine screening test, and is often diagnosed at late stages, when the tumour cells have already spread to other organs. According to Garvan Institute, each year roughly 2500 Australians are diagnosed with pancreatic cancer - and nearly 95 percent of them die within five years. If cancer is caught early and stopped before it spreads, the chance of survival becomes much higher.

To give cancer to the biosensor mouse, researchers introduced two genetic mutations responsible for creating most pancreatic cancers in humans - particularly one type that’s known to be invasive.

“What amazed us was that we could actually stop the spread of disease, keeping it local and stopping it in its tracks,” Timpson told SBS.

When they saw cancer cells starting to unzip, the researchers treated the mice with anti-invasive cancer drugs, dasatinib and saracatinib. “Within three days of treatment, we saw cells within the tumour had rezippered, and we could stabilise the primary tumour,” said Timpson.

“We’re now looking to see if we can use this beyond pancreatic cancer, and start in breast cancer, and colon cancers, for example.”

 

Promise of new cancer treatment

“We’ve actually already started discussions with large pharmaceutical companies both in Europe and Australia,” Timpson explained. For companies with various anti-cancer drugs in the development pipeline, this new biosensor mouse will become a valuable tool to better test whether a particular medication might be able to stop the disease from spreading.

Testing usually starts out in a petri dish, but this doesn’t always give a clear indication of whether the drug works, because cells can respond differently when they’re taken out of the body.

Professor Alpha Yap from the University of Queensland’s Institute for Molecular Bioscience has praised the research, calling it valuable.

“For the first time we are able to test how the E-cadherin adhesions between cancer cells respond to drugs when the cancers remain within the body,” said Yap, who wasn’t involved in the study. “This is an important contribution in the search to understand cancer and develop new treatments for it.”

Unfortunately, this approach can’t be used for cancer that’s already spread - but Timpson says the team is working on additional models. “We’re also creating other mice to look at different stages of cancer, so I would say it’s a major breakthrough in terms of tools for discovering new cancer drugs.”

The study was published today in Cell Reports.