Measuring the mechanical strength of cancer cell mucus layers provides help with treatment decisions, says Kai-tak Wan, Ph.D., associate professor of engineering at Northeastern University. His work suggests that inhibiting the formation of this mucus layer could help drugs penetrate tumors.
The article, “Glycoprotein mucin molecular brush on cancer cell surface acting as mechanical barrier against drug delivery,” appears in Applied Physics Letters.
Healthy tissues naturally secrete mucus to protect against infection, but cancer cells produce far more mucus. Uptake of cytotoxic drugs by tumor cells is limited by the dense dendritic network of oligosaccharide mucin chains that forms this mechanical barrier. Over-expressed mucus also makes it easier for cancer cells to break away from surrounding cells and metastasize.
Dr. Wan’s research partner, Robert B. Campbell, Ph.D., an associate professor of pharmaceutical sciences at Massachusetts College of Pharmacy and Health Sciences, was investigating the use of chemical agents that limit the formation of the mucus barrier so medicines can get through. To determine how well those agents work, Dr. Wan used an atomic force microscope to push against the mucus barrier. The less resistance it encountered, the less tangled the barrier.
The chemotherapeutic agent benzyl-α-GalNac for inhibiting glycosylation was shown to be effective in reducing the mechanical barrier. Dr. Wan found that suppressing the formation of mucus sidechains significantly reduced the energy needed to pierce the mucus barrier in lung, breast, colorectal, pancreatic, and wild type ovarian cancer cells.
Yet the treatment registered barely any change in multidrug-resistant ovarian cancer cells. Dr. Wan thus suggests that the mucus layer formed by the two types of cells reacts differently to the same chemical treatment.
“How this phenomenon is related to biochemistry is unknown at this stage, but it tells us what we should be looking at in future research,” Dr. Wan concludes.