Study from U of G identifies key protein in cancer metastasis

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Professor Jim Uniacke –
Photo courtesy of the University of Guelph.

The University of Guelph researchers have made a discovery during one of their ground-breaking studies. They have identified a protein known as cadherin-22 that binds cancer cells together and allows them to invade tissues. Hindering this protein showed signs of reduction in metastatic cancer patients for breast and brain cancer cells by up to 90 per cent.

“Cadherin-22 could be a powerful prognostic marker for advanced cancer stages and patient outcomes,” says lead author Prof. Jim Uniacke, department of molecular and cellular biology. “If you can find a treatment or a drug that can block cadherin-22, you could potentially prevent cancer cells from moving, invading and metastasizing.”

This study was published in the journal Oncogene and looks specifically at hypoxia in tumours. More solid cancer tumours that are depleted of oxygen, are difficult to treat and replicate at a faster rate. The researchers from the university discovered from the analysis of more than 100 patients with breast or brain cancer that there was a link between the quantity of cadherin-22 and the level of hypoxia in a tumour itself. The more hypoxic the tumour was, the higher the protein count of cadherin-22.

Until now, little was known about how oxygen-deprived cancer cells bound together and interacted to spread. The U of G researchers found that it is precisely under conditions of low oxygen that cancer cells trigger the production of cadherin-22, putting in motion a kind of protein boost that helps bind cells together, enhancing cellular movement, invasion, and likely metastasis. The protein is found on the outside of cells and allows hypoxic cancer cells to migrate together.

Scientists have known for decades that hypoxia plays a role in tumour growth and metastasis, as well as a poor patient outcome. Uniacke and his team identified that cadherin-22 plays an integral part in the advancement of cancer cells.

“We found that the more hypoxic a tumour was, the more cadherin-22 there was in the area of the hypoxia,” says Uniacke. “Not only that but the more cadherin-22 that there is in a tumour, the more advanced the cancer stage and the worse the prognosis is for the patients.”

The researchers used an incubator to monitor cancer cells in a low-oxygen environment comparable to a tumour, where the protein cadherin-22 had been removed via molecular tools. The cancer cells failed to spread.

“One very powerful and common tool in cell and molecular biology labs is, you can remove a protein from a cell and see how that cell behaves without it,” says Uniacke. “We culture our cancer cells in this very low-oxygen environment, and they start behaving like they are inside a low-oxygen tumour. Because a cancer tumour has a poor blood supply, it doesn’t get the proper oxygen. The cancerous cells need to change their behaviour, changing what proteins they synthesize in order to try to adapt to these environments.”

These findings offer vital insights into the aggression and migration of cancer cells. Uniacke received $688,500 from the Canadian Institutes of Health Research this past May for his low-oxygen tumour study.

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