Detecting oral cancer in its earliest stages can
save the lives of the nearly 40,500 people diagnosed annually. But
early detection has been difficult.

Case Western Reserve University School of Dental Medicine
researchers discovered a biomarker, called human beta defensin-3
(hBD-3), which may serve as an early warning. The defensin is present
in all oral cancers and associated with the early stages of oral
cancer.

"Using the biomarker to detect oral cancer holds potential for
saving lives when the cancer is most curable. Annually some 10,000
people die from this cancer," said Ge Jin, assistant professor of
biological sciences at the dental school.

He led the study, "An Antimicrobial Peptide Regulates
Tumor-Associated Macrophage Trafficking via the Chemokine Receptor
CCR2, a Model for Tumorigenesis." The Public Library of Science
published the research in PLoS ONE.

Oral cancer first appears as white or red lesions in the mouth,
the same as noncancerous lesions.

Often, the lesions are not biopsied, and cancer is not
discovered until it becomes apparent in its later stages, when it has
metastasized to other organs. Such a late-stage diagnosis is generally
fatal and can result in costly surgeries and treatments or
disfigurement that may include removing parts of the tongue, jaw and
cheek. All this can be avoided with early removal of the lesion.

The hBD-3 biomarker is one of many innate immune peptides found
in the epithelial lining of the mouth. In a normal, healthy oral
cavity, hBD-1, -2 and -3 ward off the hundreds of bacteria that
constantly challenge the human immune system in the mouth.

While hBD-1 and -2 are on the frontline defense, hBD-3 is only
found in the basal layer where oral cancers grow. The researchers
report that the hBD-2 disappears and only hBD3 is present when a
cancerous tumor progresses.

Jin added that the lone presence of hBD-3 made the research team
question its role on tumor growth and found it attracts other molecules
that actually help the cancerous tumor grow and eventually spread to
other parts of the body.

It appears hBD-3 plays a role in the development of the
chemokine receptor called CCR2 that recruits tumor-associated
macrophage cells to infiltrate the tumor site and stimulate tumor
growth. The tumor-associated macrophages and other molecules release
growth factors that encourage the progression of the tumor. Eventually
tumor cells break away, travel and spread the cancer to other places in
the body.

"This is the first time that we have evidence that CCR2, too,
has a role in oral cancer growth," said Jin.

The researcher plans to continue studying the role of hBDs in
oral health and to develop diagnostic tools that use the biomarker to
detect early cancer.

Other project researchers are: Hameem I. Kawsar, Stanley A.
Hirsch, Xun Jia, Santosh K. Ghosh, Zhimin Feng, Aaron Weinberg from
Case Western Reserve University; Qing Yin Zheng from University
Hospitals Case Medical Center; Chun Zeng and Aimin Zhou from Cleveland
State University; and Thomas M. McIntyre, Learner Research Institute at
the Cleveland Clinic College of Medicine of Case Western Reserve
University.

Case Western Reserve University is among the nation's leading
research institutions. Founded in 1826 and shaped by the unique merger
of the Case Institute of Technology and Western Reserve University,
Case Western Reserve is distinguished by its strengths in education,
research, service, and experiential learning. Located in Cleveland,
Case
Western Reserve offers nationally recognized programs in the Arts and
Sciences, Dental Medicine, Engineering, Law, Management, Medicine,
Nursing, and Social Work. http://www.case.edu