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Sunday, April 14, 2024

Use of chemical analytical tools shows insights into cancer metastasis

Lebrilla Lab studies biomolecules as potential method for improvements in cancer treatment, diagnosis

At the intersection of analytical chemistry and disease lies the Lebrilla Lab. Led by Carlito Lebrilla, a distinguished professor in the Chemistry Department, the team developed very rapid and accurate methods for characterizing biomolecules related to health, nutrition and disease. 

Glycans are one of the biomolecules the lab has been studying for almost 20 years. They are polysaccharides or sugar chains that attach to the proteins on a cell’s membrane. The attachment of glycans results in changes to cell functions, which are not well understood due to the difficulty of studying glycans themselves. The Lebrilla lab has been revolutionizing the way glycans are understood and studied by using unique analytical tools that allow them to measure, characterize and identify glycans.  

Such tools include nanoflow liquid chromatography, which separates a mixture of glycans into smaller sample sizes. High resolution mass spectrometry gives each glycan compound a unique identity and allows researchers to know the constituent parts of the polysaccharide.

“The key is that it is super difficult to measure the glycans and that is the greatest strength of their lab and why this lab is so important for the scientific community in general,” said Fernando Fierro, an assistant professor in the Department of Cell Biology and Human Anatomy. 

A recent study conducted at their lab shows the success of their analytical tools. The study identified the important role glycans have in the spread, or metastasis, of human cholangiocarcinoma or bile duct cancer. 

“We were interested in looking at the cholangiocarcinoma cell surface to identify specific molecules that may promote the aggressiveness of the disease” said Diane Dayoung Park, a postdoctoral researcher in the Lebrilla Lab, via email.

While bile duct cancer is not common in the U.S., it is exceedingly prevalent in Southeast Asia due to the consumption of undercooked or raw fish infected with a parasite called liver flukes. Through a collaboration with a lab at Khon Kaen University in Thailand, the researchers obtained cancer cells to analyze and conduct their studies on.  

They were able to deduce that cells with high amounts of mannose glycans, a specific type of glycan, were found to migrate faster, more frequently and through barriers non-cancer cells could not navigate through. It was determined that the attachment of high mannose glycans modified the cell functions to a degree in which metastasis would occur.

“Cancer cells all have the same proteins as non-cancerous cells but it is the change in the modifications, the glycans, that result in the change in cell function,” Lebrilla said. 

Additionally, the lab tested an antibody, a specific compound that interacts with the high mannose glycan. As the antibody targeted the high mannose glycan cells and reduced the levels of mannose, the cells stopped moving as fast. These results further showed the effect of high mannose glycans on cell function and its ability to induce cell spread.

The implications of this research could be profound for both the diagnosis of cancer and the treatment options available. One of the main challenges for treating cancer is its ability to metastasize. Removal of a tumor is most effective at halting cancer if it has not yet spread. Once cancer has metastasized, treatment is far more difficult. With a deeper understanding of glycans, it would be possible to develop treatments targeting cancer cells that are prone to spreading. 

“The problem right now is that once the cancer metastasizes it is difficult to cure,” Lebrilla said. “But if you can slow down that spread, then perhaps you can be more effective at treating it.”

Lebrilla also sees a future where glycans are used as a diagnostic tool and has made this into a reality with InterVenn, a company he co-founded. Based in the Bay Area, InterVenn is developing a blood test for ovarian cancer. The blood test uses glycan as a biomarker, which specifically would indicate the presence of ovarian cancer. They hope to make the test extremely efficient so that a simple blood prick could identify the cancer. InterVenn hopes to develop diagnostic methods for other types of cancers as well. 

“We need to be able to look at more types of cancer but we think that for many cancers this is a way that they spread and we want to find out what the mechanisms are for other cancers,” Lebrilla said.

Projects such as InterVenn highlight the innovative field the Lebrilla Lab exists in. Through the help of their analytical tools and glycan research, the future of cancer treatment and diagnosis may be drastically improved.

Written by: Alma Meckler-Pacheco — science@theaggie.org 


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