Laboratory studies conducted at Johns Hopkins revealed that human colorectal cancer tumor cells presented high levels of a protein called beta-1,4-galactosyltransferase-V (beta-1,4-GalT-V), compared to normal samples. Blocking the protein and its byproducts resulted in a stall of mutated cells proliferation.
“We know that beta-1,4GalT-V is highly and specifically enriched on the endothelial cells in the lining of blood vessels, in cancer tissue”, explained study author Subroto B. Chatterjee, M.S., M.Sc., Ph.D. “If you treat these cells with a drug that targets beta-1,4GalT-V, it will go and attack the endothelial cells that have this protein, and hopefully it will neutralize their activity”.
The protein is also responsible for producing lactosylceramide, a fat that can generate superoxides, leading to an increase in new cells and blood vessels that cancers use to grow and spread. The two molecules can now be added to a growing list of biomarkers, such as NMT1, APC and TP53, all known to indicate the risk of developing cancer.
With more than 1.8 million cases just in 2018, colorectal cancer remains the third most prevalent form of malignancy. The most common detection test is screening colonoscopies, which usually don’t begin until a person turns 50. “So, there is a great need for reliable biomarkers for early-stage diagnosis of colorectal cancer”, added Dr. Chatterjee.
Initial testing was done on a number of 24 tissue samples, which showed strong reactivity to beta-1,4GalT-V antibodies. An enzyme-linked immunosorbent assay (ELISA) test to detect and measure antibodies in 21 of these samples found levels of protein six times higher for affected portions compared to normal areas on the same sample. Lactosylceramide numbers were also elevated, by approximately 2.2 times.
Previous studies had demonstrated that daily treatment with D-PDMP (D-threo-1-phenly-2-decanoylamino-3-morpholino-1-propanol), an inhibitor that targets cancer pathways, could reduce kidney tumors in mice, by inhibiting the activity and mass of beta-1,4GalT-V. The team then tested lab-grown human colorectal cancer cells called HCT-116 with D-PDMP and found that treatment led to reductions in beta-1,4GalT-V and an increase in cell death.
“This provides evidence that beta-1,4GalT-V is a target for cell proliferation, and that we can block the cycle of cell proliferation by using this D-PDMP compound, at least in cell-based testing”, concluded Chatterjee.
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