Every living cell has a membrane covered in chains of sugar molecules, called glycans. Recently, researchers from Griffith University in Australia and their Swiss collaborators have shown that glycan patterns differ between ovarian cancer cells that will spread throughout the body, and more stable primary tumour cells. These differences are key to cancer being able to move to other parts of the body, through a process called metastasis1.
“These sugars make up a biological code, the glycome, that is as essential for life as the genetic language of the genome,” explains Mark von Itzstein, Director of the Institute for Glycomics at Griffith University in Queensland, Australia. “But unlike the genome it’s a very dynamic language that changes as we age. And it’s a language written predominantly on, and anchored to, the cell surface.”
The 2022 finding also identified an enzyme that appears to change the glycans so that the cells can break free from solid cancers and spread to other parts.
“When we modify the enzymes that change these glycans, the cells automatically become more metastatic or less metastatic,” explains Arun Everest-Dass, the Griffith research lead on the findings. This result could offer a way to identify cancer cells that are more likely to spread, he says, and could even help researchers modify or develop treatments.
Sugars are carbohydrates – a type of molecule more associated with supplying cells with energy than of having any higher function. But the more that researchers look at different types of sugar-coated cells, the more they realise that these carbohydrate chains play many important roles from cell signalling to controlling aspects of cell behaviour.
In their study, published in collaboration with researchers led by Francis Jacob, based at University of Basel, Switzerland, von Itzstein and Everest-Dass used an advanced imaging technique based on the principle of mass spectrometry to build up a picture of how glycans were arranged on the surface of primary ovarian tumours. The disease is one of the most lethal cancers because it is typically not detected until the cancer is already well advanced and has spread to the abdomen.
Next, they looked at how glycans differed on patient cancer cells that were more mobile and so able to travel beyond the ovaries. The team found that glycan patterns were different on the mobile cells, suggesting that primary tumour cells needed to somehow change their surface glycans to break free from solid cancers if they are to travel to spread the disease to other parts.
They went on to identify the enzyme used by the cells to alter the glycan code in this way. And when the international team of researchers used gene editing techniques to disable this enzyme, they saw that the cancer cells could no longer change their glycan coatings, and so could not metastasize, opening up a potentially fertile path for future cancer research.
The cutting-edge imaging facilities at Griffith University were central to the discovery, von Itzstein adds, and could be used for other applications, including to explore cell plasticity in other cancers. “Given this technology has really come of age now it offers a truly remarkable opportunity and training ground for the next generation of scientists,” he says.