Cancer research: Your cells’ sugar diet
April 25, 2016
For Kevin Yarema, research is sweet.
Yarema, an associate professor in Biomedical Engineering, has focused much of his efforts on metabolic glycoengineering — the ability to manipulate cells’ natural process of ingesting sugars and converting them into complex sugar structures that cover the cell surface.
“Cells can change these sugars depending on what they’re doing,” Yarema says. Similar to how people change clothes for a wedding versus playing rugby, he says, cells constantly change their sugar coatings. Cancer cells, for example, are able to use about 200 times more glucose than normal cells, which often results in different sugars displayed on their surfaces than healthy cells.
Yarema’s lab has taken a metabolic approach to try to alter pancreatic cancer and brain cancer cells, feeding them unique sugar compounds created in the lab to change how they process and display sugars.
“We can go in several different directions,” Yarema says. “One is to try to tweak the types of sugars normally found on a cancer cell, to make it be more like the sugars on a healthy cell … It could be a benign way to treat cancer.” In other work, his lab is adding non-natural chemical groups into sugars that cells ingest with the hope that they would change the cell surface so it would be chemically distinct from a normal cell. “That opens up possibilities that the immune system would attack it, or that we could make a drug or diagnostic agent that would recognize the unique chemistry of a cancer cell to treat it that way.” In a recent paper, treating drug-resistant pancreatic cancer cells with both typical tyrosine kinase inhibitor drugs and a compound developed in his lab resensitized the cancer cells so they once again responded to drug treatment.
With National Cancer Institute funding, Yarema’s team also is studying the downstream effects of what happens when cells use glucose, looking for molecular targets to block so they can’t drive cancer development. “We’re not trying to stop cancer cells from using all this glucose. We’re trying to stop them from doing bad things with it via signaling.”
The sugar analogs created in his lab have the added bonus of knocking down inflammation, making them potentially useful for diseases beyond cancer. For example, work published recently in the journal Biomaterials found that one compound could intercept biosynthetic pathways that make extracellular matrix material, reduce inflammation, and rebuild cartilage in a rat model of osteoarthritis. Additional studies in progress suggest the compounds can also promote healing in cardiovascular disease and in muscle diseases such as Duchenne muscular dystrophy and GNE myopathy.
— Karen Blum
Research paper: Biomaterials
Local delivery of a carbohydrate analog for reducing arthritic inflammation and rebuilding cartilage
Yarema Lab: Laboratory of Cell and Carbohydrate Engineering