Johns Hopkins researchers have identified a protein biomarker involved in the development of new blood vessels that could identify colorectal cancer symptoms.
In laboratory studies, investigators found that expression of the protein, called beta-1,4-galactosyltransferase-V (beta-1,4-GalT-V), was increased in human colorectal cancer tumour cells compared with normal tissue. They also observed an increase in this protein’s activity and in its product lactosylceramide, a fat that can produce superoxide’s, which lead to an increase in new cells and blood vessels that cancers can use to spread. Inhibiting the protein and its by-products halted colorectal cancer cell proliferation, therefore posing as a biomarker to detect colorectal cancer symptoms.
These results were published in Biochemical and Biophysical Research Communications.
Identifying the biomarker for colorectal cancer symptoms
The findings demonstrate that lactosylceramide could be added to a growing list of biomarkers such as NMT1, APC and TP53 in blood tests for colorectal or potentially other cancers to increase their success at early detection of disease.
lead study author Subroto B. Chatterjee, Johns Hopkins University School of Medicine, USA, explains: “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.”
“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.”
Tackling colorectal cancer symptoms
Colorectal cancer affects more than 1.4 million people worldwide, causes over 690,000 deaths and is third in prevalence of all cancer types.
The researchers highlight that screening colonoscopies usually don’t begin until a person turns 50.
One of the most common screening tests used is a stool test for colorectal cancer that is based on DNA technology. Outcomes from such tests must be accompanied by a colonoscopy. “So, there is a great need for reliable biomarkers for early-stage diagnosis of colorectal cancer.” adds Chatterjee.
For this research, a number of laboratory experiments were conducted. First, the researchers acquired 24 tissue samples archived at Johns Hopkins from colorectal cancer patients to test the samples’ response to antibodies against beta-1,4GalT-V, finding strong reactivity.
An enzyme-linked immunosorbent assay (ELISA) test to detect and measure antibodies in 21 of these samples found an approximately 6.5-fold increase of beta-1,4GalT-V in colorectal cancer tissues compared with visibly normal areas within the same samples.
Investigators also noted a 2.25-fold increase in lactosylceramide synthase activity in colorectal cancer samples compared with normal colon cells. Additional testing found elevated expression of several genes previously associated with colorectal cancer, such as APC, TP53 and NMT1, in the samples.
“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,” Chatterjee concludes.
“It shows the potential for the application of this compound in perhaps multiple types of cancers.”