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Posted on Jan 07, 2019, 5 p.m.
A protein involved in cell proliferation and development of new blood vessels that may serve as marker for early detection of colorectal cancers has been identified by Johns Hopkins researchers, as published in the journal Biochemical and Biophysical Research and Communications.
Expression of beta-1, 4-galactosyltransferase-V was found to be increased in human colorectal cancer tumor cells as compared to normal cells in laboratory studies, as well as an increase in its activity and its product lactosylceramide that produces superoxides, which leads to increases in new cells and blood vessels cancers can use to spread; inhibiting beta-1, 4-GalT-V and its byproducts were observed to halt colorectal cancer cell proliferation.
According to the researchers their findings demonstrated that the protein and lactosylceramide should be added to the list of biomarkers in blood testing for colorectal or potentially other cancers to increase success at early detection. Beta-1, 4-GalT-V is highly and specifically enriched on endothelial cells in cancer tissue blood vessel lining; treating these cells with a drug targeting the protein it will attack endothelial cells with the protein and hopefully neutralize activity.
Upwards of 1.4 million people are estimated to be affected by colorectal cancer worldwide which causes over 690,000 deaths, and is ranked third in prevalence of all cancer types. Screening colonoscopies typically don’t begin until the age of 50, of which one of the most common used is a stool test based on DNA technology that must be accompanied by a colonoscopy; making a great need for reliable biomarkers for early stage diagnosis.
Tissue samples were acquired from colorectal cancer patients to test responses to antibodies against bet-1, 4-GalT-V which produced strong reactivity. ELISA testing was used to detect and measure antibodies in the samples which found approximately 6.5 fold increase of the protein in colorectal cancer samples compared with normal samples. A 2.25 fold increase in lactosylceramide synthase activity was noted to be observed in the colorectal cancer samples; additional testing revealed elevated expression of several genes previously associated with colorectal cancer including APC, TP53 and NMT1.
Building on findings from an early study in 2013 published in the journal PLoS One demonstrating daily treatment with D-PDMP for 4 weeks reducing size of kidney tumors in mice via inhibiting activity and mass of beta-1, 4-GalT-V, the team tested lab grown human colorectal cancer HCT-116 cells to be treated with D-PDMP. Over a period of 24 -96 hours cells treated with D-PDMP were observed to display significant reduction in beta-1, 4-GalT-V and increased cell death compared to controls.
According to the team these results provide evidence that beta-1, 4-GalT-V is a target for cell proliferation that can be blocked via treatment with the compound D-PDMP, using data from theri cell based testing; and it shows potential for the application of the compound to be used in other types of cancers.
Materials provided by Johns Hopkins Medicine.
https://www.sciencedaily.com/releases/2019/01/190107142209.htm
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Journal Reference:
Subroto B. Chatterjee, Jennifer Hou, Veera Venkata Ratnam Bandaru, Maryam Kherad Pezhouh, Abul Ala Syed Rifat Mannan, Rajni Sharma. Lactosylceramide synthase β-1,4-GalT-V: A novel target for the diagnosis and therapy of human colorectal cancer. Biochemical and Biophysical Research Communications, 2019; 508 (2): 380 DOI: 10.1016/j.bbrc.2018.11.149
