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Glyco-Chemistry Laboratory, Wollongong University

Lifting the lid on cancer’s sweet tricks

They come dressed in disguise. Looking like one of us, we don’t notice them until it’s too late and they’ve already begun to wage a deadly war.

While this may seem like the plot of a sci-fi film in which aliens invade Earth, this story is actually not science fiction. It’s a war fought within our bodies as cancers, hidden under protective disguises encroach on our healthy cells, posing as friend instead of foe.

The disguise? Sugar.

Well, not the sugar you add to your coffee or tea but a special type of sugar known as sialic acid. After glucose, sialic acid is our body’s most important sugar and is found in the highest amounts in human breast milk. Unfortunately, as we age the amounts of sialic acid reduce significantly. Danielle Skropeta, Associate Professor at the Glyco-Chemistry Laboratory, Wollongong University explains that cancers have discovered the importance of this sugar and use it as a disguise to trick our cells into allowing them access.

“They coat themselves with up to 50% greater amounts of sialic acid than comparable normal tissues to give the appearance of a healthy young cell to avoid immune detection,” Danielle explains.

Sialylation, is the addition of sialic acid to molecules on the cell surface via sialyltransferase (ST ) enzymes. This is vital for cell function. However, when sialylation goes awry and there is marked upregulation of ST activity, it is often a hallmark of cancer. Even more disturbing is that this is directly correlated to an increased potential for metastasis and subsequently, poor patient prognosis.

The team at Glyco-Chemistry laboratory at Wollongong University are working in collaboration with IHRMI and in a new partnership with Australia’s Nuclear Science and Technology Organisation (ANSTO) on how to prevent cancers from building this protective coat of sialic acid. By creating ST inhibiting molecules, the team aims to stop the cancer-cells from spreading by revealing them to the immune system.

“By removing the key carbohydrate, the body’s immune cells can be more effective in removing the cancer cells because they no longer have their protective layer,” Danielle explains.

“The benefit of these ST inhibiting molecules is they are less toxic to the body. The sugars on the tumour cell surface are not essential for survival but they are crucial for the tumour to spread. So drugs based on this strategy, that is anti-metastatic drugs, are likely to have fewer side effects than typical toxic chemotherapeutics that are aimed at killing cells but end up also affecting normal cells as collateral damage.”

Looking to the deep sea

Danielle and her team are also looking deep into the ocean for answers in the fight against cancer. In a unique partnership with the oil and gas industry, the team is leading the way in understanding how deep-sea organisms and deep-sea derived products can be used in medicinal chemistry. Accessing specialised robots called remotely operated vehicles (ROVs) which are operated at the surface and can access depths of up to 3500 metres, the SERPENT team collected sea sponges (at depths of 200-1000m) to explore new types of chemical scaffolds.

“Our research shows that deep-sea natural products have an incredibly high ‘hit’ rate, in particular against cancer. This means that the percentage of natural chemicals exhibiting anticancer activity discovered in deep-sea samples, in some cases as high as 50-75 per cent of samples assessed, far exceeds that typically seen in natural product-based drug discovery,” says Danielle.

Studying the benefits of seaweed

Another area the team is researching is the use of seaweed polysaccharides on wound healing, nutrition and skin care applications. While, at first glance this may seem distant to cancer research, Danielle explains that wound healing and cancer are at two ends of a very similar biological process so what is learnt in wound healing may have applications in cancer.

“In wound healing applications, we are trying to promote cell migration of the right type of cells such as fibroblasts and keratinocytes that play critical roles in the wound healing process. However, in cancer we are trying to stop the spread of the wrong types of cells, i.e. cancer cells,” Danielle explains.

The team

The Glyco-Chemistry lab team are doing fascinating work across a wide range of projects and it is fitting to recognise Danielle Skropeta whose leadership has seen her PhD students move into an equally wide range of positions outside of the university.

“Not all students want to stay in research so I ensure that I mould the projects around their interests. One of my students went on to do the Homeward Bound Antarctica expedition and now works for Questacon as a Science Communicator while others have gone into the business side of chemistry.”

Danielle was also recently awarded best practice for PhD supervision by the University as well as a senior international teaching fellowship by AdvanceHE.

Although the team is small, ranging between six to eight people, the Glyco-Chemistry lab are making significant contributions in cancer research through their novel and innovative approaches.

By Linda Music