The holy grail of clinical diagnostics would be a completely noninvasive technique that can identify disease with exceptional accuracy. Unfortunately, science has yet to achieve this almost essential goal. However, new research from Johns Hopkins scientists may provide the crucial data required to take a big leap toward complete noninvasive diagnoses.
Imaging tests such as mammograms or CT scans can often detect tumor growth within tissues, but determining if that growth is cancerous almost always requires a biopsy in order to study cells from the mass directly.
Conversely, the results from the current study would suggest that MRI’s could make many biopsies obsolete by tuning the machines to detect the glycosylation pattern of a specific glycoprotein that is often shed by the outer membranes of cancerous cells.
"We think this is the first time scientists have found a use in imaging cellular slime," said Jeff Bulte, Ph.D., professor of radiology and radiological science in the Institute for Cell Engineering at the Johns Hopkins University School of Medicine and senior author on the study. "As cells become cancerous, some proteins on their outer membranes shed sugar molecules and become less slimy, perhaps because they're crowded closer together. If we tune the MRI to detect sugars attached to a particular protein, we can see the difference between normal and cancerous cells."
The findings from this study were published recently in Nature Communications through an article entitled "Label-free in vivo molecular imaging of underglycosylated mucin-1 expression in tumour cells."
Previous studies have found that the glycoprotein mucin-1 is overexpressed and underglycosylated in most malignant adenocarcinomas of epithelial origin, for example, colon, ovarian, and breast cancer. Moreover, aberrant expression of mucin-1 has been seen in almost 65% of the 1.4 million tumors diagnosed each year in the United States.
Dr. Bulte and his team wanted to take advantage of these telltale signs for tumor growth by fine-tuning an MRI technique that detects a unique interaction of glucose with its surrounding water molecules without administering dyes. The researchers were able to compare mucins, with and without their sugar moieties, to observe how the MRI signal changed. The team then used the same technique to analyze four types of in vitro cancer cells, in which they were able to detect markedly lower levels of mucin glycosylation in comparison to normal cells.
"The advantage of detecting a molecule already inside the body is that we can potentially image the entire tumor," explained Xiaolei Song, Ph.D., research associate in Dr. Bulte's laboratory and lead author on the study. "This often isn't possible with injected dyes because they only reach part of the tumor. Plus, the dyes are expensive."
The next step for the Johns Hopkins group is to see if they can distinguish a variety of cancerous tumors in living mice. Though Dr. Bulte and his team are optimistic about their current findings they did caution that there is much more testing that needs to be done to prove that the technique has value for clinical diagnostics in human cancers.