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Advances in the sciences have made it easier than ever to live with and survive various kinds of cancer. One of the lingering challenges that remains is metastasis, or the ability of cancer cells to migrate to new pathological sites within the host’s body.

October is National Breast Cancer Awareness Month. Too many of us have been touched by breast cancer and other forms of this disease. The good news is, the research shown here will go a long way in helping us understand how cancer moves in the human body and in helping us halt that process in its tracks.

How Does Cancer Spread, or ‘Metastasize’?

The spread and influence of an “ordinary” cancerous tumor into neighboring hosts can be contained and removed. A tumor which has metastasized, however, becomes a risk to other organs and tissues in the body as it travels.

Until recently, the mechanism behind cancer cells’ “mobility” — the ability to travel to new parts of the body — wasn’t understood and so couldn’t be stopped or defended against. Recently published research sheds a light on how this works and how our cancer treatment techniques may change as a result.

Why Study Proteins?

Proteins function as the building blocks of life. To be more specific, they’re some of the first “blocks” that DNA “figured out” how to direct and build with. We understand, essentially, that the physical characteristics of all life, like muscles, hair and skin, are genetics expressed through protein.

When cancers infect the human body and turn it toward its own ends, those cancers use proteins too. And until now, researchers weren’t sure which proteins, specifically, were helping cancerous cells to achieve mobility through metastasis. What makes them able to travel?

This research concerns the transition of cells between their “epithelial” variants and their “mesenchymal” variants. Epithelial cells stay where they are in the body and continue performing their current function in conjunction with the surrounding cells. Mesenchymal cells have no such obligations, and so get swept away by the blood stream to infect other parts of the body.

The questions are:

• Which proteins facilitate this transition?
• Can we isolate those proteins and prevent cancers from using them to metastasize?

To answer these questions, associate professor Nurhan Özlü, representing the Department of Molecular Biology and Genetics at Koç University, and a large, multidisciplinary team, studied thousands of proteins. The stakes are clear, as more than 90% of cancers that occur in the human body happen in its epithelial cells.

The only other process where the epithelial-to-mesenchymal transition takes place is during embryonic development. Functionality-wise, epithelial cells occur in tissues and regulate how nutrients and blood are transported and implemented by our body systems and our tissues and organs. Until now, we hadn’t been able to witness these processes at the protein level.

So what did the research team find out about this process?

What Does the Research Say and What’s Next?

The research team used epithelial cells from the human breast to build “protein profiles” of the cells as they passed from the epithelial to the mesenchymal states. Differences between these profiles yielded hundreds, then close to two-dozen, final candidates that were active in the epithelial and mesenchymal states to varying degrees.

From there, trial and error yielded a final two: DNAJB4 and CD81. Animal testing involved suppressing these two proteins in mice. Cancerous tumors grew far slower and smaller in subjects which had these two proteins suppressed. Being a surface protein, it is expected that study on CD81 will soon begin apace and yield useful results.

Finding treatments that make chemotherapy less necessary and its manifold side-effects less unpleasant is always a welcome proposal. And discovering drugs that can slow or stop metastasis would mark a milestone in anticancer research and give new hope to thousands of people every year.

Even here, in October 2019, breast cancer has a long shadow. There are around 245,000 newly diagnosed cases of breast cancer in the U.S. every year. Some 41,000 of these cases result in death. Early detection, liquid biopsy and precision and gene therapies have all helped improve patient outcomes and bring breast cancer rates down, but the struggle continues.

Importantly, the Koç University research group has made their findings open and available to all peersfor appraisal and additional study.

The implications for drug targeting studies in breast cancer and other types of research are already generating a lot of interest now that other researchers know which proteins to manipulate, out of tens of thousands or even millions of candidates.

Written by Kayla Matthews, Productivity Bytes.