Cellular signals discovered between saliva and pancreatic tumors

Pancreatic cancer biomarkers have been definitively validated in saliva. This finding may be a major step toward enabling clinicians and oncologists to detect pancreatic cancer with a simple risk assessment using saliva.

Pancreatic cancer is one of the deadliest forms of cancer. Most of those with the disease die within the first year of diagnosis, and only 6% will survive 5 years. The disease is typically diagnosed through an invasive and complicated biopsy.

To date, salivary biomarker panels have been successfully developed for cancers of the breast, ovaries, lungs, and pancreas. However, researchers in the field of salivary diagnostics are still attempting to understand how biomarkers produced by other parts of the body ultimately appear in the mouth. Scientists have surmised that RNA molecules—which translate genetic code from DNA to make protein—are secreted into extracellular spaces and act as an information signal system, representing an innovative model in intercellular signaling.

With this understanding, a research team led by David Wong, DMD, DMSC, of the School of Dentistry of the University of California at Los Angeles, was able to demonstrate that tumor-derived extracellular RNA molecules are transported through organelles called exosome vesicles that originate at the source of the tumor and are reprocessed into saliva as biomarkers. To prove it, the researchers examined mice models with pancreatic cancer whose saliva showed evidence of biomarkers for pancreatic cancer.

When the scientists inhibited the production of exosomes at the source of the tumor, the researchers found that the pancreatic cancer biomarkers no longer appeared in the mouse's saliva. Their discovery supports their claim that tumor-derived exosomes provide a mechanism in the development of disease-specific biomarkers in saliva. Their findings were published in the Journal of Biological Chemistry (2013; doi:10.1074/jbc.M113.452458).

"This paper is significant because it provides credibility to the mechanism of systemic disease detection in saliva," said Wong. "We have been able to substantiate the biological connection between systemic disease and the oral cavity."

The team's findings come on the heels of a $5 million award that Wong received from the National Institutes for Health's Common Fund, which is a strong statement that saliva is proving to be scientifically credible for the detection of systemic disease and is advancing toward clinical maturation.

"Dr. Wong and his team have provided verifiable evidence to fully explore the use of salivary biomarkers for the detection of life threatening disease in a way that is noninvasive and doesn't cause pain for the patient," said No-Hee Park, DMD, PhD, and dean of the School of Dentistry at UCLA. "This new paper truly confirms a mechanistic tie between systemic diseases and their oral manifestations."

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