Protein sticks cancer cells to surrounding tissue to slow their spread
Surgical removal or chemotherapy might prove effective at eliminating an initial tumor, but often cancer cells can break away and give rise to secondary growths around the body. Known as metastatic cancer, this is actually the primary cause of death from the disease, motivating a great deal of research into ways to stop the spread. A new study has turned up a new target, unearthing a protein that prevents cancer cells from migrating by sticking them to surrounding tissue.
While the dangers of metastatic cancer are well-known, what isn't so clear is why some patients experience it following treatment for a primary tumor and some do not. Lingering cancer cells can migrate to other parts of the body through the blood or lymphatic vessels to form new tumors, and the authors of the new study are seeking to both learn more about and possibly intervene in this process though a protein called MFSD1.
The team, made up of scientists from Austria's Institute of Science and Technology and the University of Zurich, had previously shown that this protein has a role to play in cell migration through experiments on fruit flies, one of the most commonly used models for biomedical research due to their short life cycle and the many genes and biological functions they share with humans. The latest study focused on mice, with the scientists engineering cancer cells that lacked this protein.
This indeed caused the cancer cells to travel much faster than those possessing the protein, indicating that MFSD1 plays a preventative role in cell migration. This effect was observed in living mice with breast, colon and skin cancer.
“In the absence of MFSD1, there was a strong increase in metastasis,” said study author Daria Siekhaus.
To dig into the reasons why, the scientists conducted a type of stress test on cancer cells both with and without the MFSD1 protein. This involved using a tiny rubber tool to scrape the cells off the surface of a Petri dish, with those containing the MFSD1 protein quickly dying due to the mechanical stress. Those without the protein, however, largely remained intact, leading the team to conclude that the cells lacking MFSD1 could more readily enter and travel through the bloodstream.
“We wanted to know why lower MFSD1 levels were beneficial to the tumor apart from allowing them to move more freely," said first author Marko Roblek. "As cancer cells travel through the blood for example, they experience a lot of mechanical stress."
Through their observations, the team showed that MFSD1 has these effects by maintaining receptors on the cell surface called integrins, which make the cells adhere to one another and also to the dense surrounding network known as the extracellular matrix. Tumor cells lacking MFSD1 therefore don't as readily recycle certain types of integrins.
“The result is, that the cells stick less to the surrounding tissue and each other, which makes it easier for them to migrate," said Siekhaus.
Though the experiments were carried out in mice, the team also explored the role of MFSD1 in human subjects by examining data on cancer patients. This revealed a correlation between levels of the protein and the subject's prognosis.
“We’ve seen that patients suffering from specific forms of breast, gastric and lung cancer who had lower levels of MFSD1 had a worse outcome," said Roblek. "A high level of MFSD1 seems to be protective – it works like a suppressor of tumor metastasis."
The team's discovery lays the groundwork for new forms of treatment that target MFSD1, potentially elevating its levels to suppress the spread of metastatic cancer. Interestingly, the scientists also note that it could be used to guide treatments by revealing how aggressive a cancer may be, if they can identify the genes encoding for the MFSD1 protein.
“If this marker becomes more established, doctors can use it to help classify how aggressive the cancer is and to decide between different treatment options," said Siekhaus.
The research was published in the journal Frontiers in Oncology, while the short video below offers a look at a team's experiments.