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Immune Peptide Shows Potential to Help Diagnose Oral Cancer

September 24, 2009

Linkage disequilibrium log for HBD-1Several years ago, a team of NIDCR supported scientists discovered something quite interesting about cultured oral keratinocytes, cells that form the lining of the mouth and its soft tissues. The scientists confirmed that when pathogens challenge oral keratinocytes, these cells produce a variety of short antimicrobial peptides called β-defensins. What made the discovery interesting is that the β-defensins were differentially expressed when exposed to different immune signaling molecules. The implication being, not all β-defensin responses are the same. This finding matched up well with the many tasks that these peptides perform, from serving as the keratinocyte’s first line of defense to signaling nearby white blood cells to attack an invading pathogen. The finding also made sense on the DNA level. Defensins arise from 28 putative DNA coding regions that could be variably transcribed to suit the cell’s immediate needs. As members of the group later wrote, “This heterogeneity suggests that different phenotypic profiles exist that may affect an individual’s susceptibility or resistance to disease.”

In the October issue of the journal Oral Microbiology and Immunology, the researchers take their discovery an intriguing step further. The finding arises from an earlier unpublished observation in their laboratory. That is, cultured oral squamous cell carcinoma cells (OSCC), which stem from normal oral keratinocytes, variably expressed a β-defensin gene called HBD-1. To follow up on this lead, the group collected 19 recognized OSCC cell lines, established their own normal keratinocyte cells lines from the gingiva, or gums, of healthy volunteers, and asked two questions. Do normal and cancer cell lines differ in their baseline and induced expression levels of the β-defensin genes HBD-1, -2, and -3? If so, as a first step in explaining this phenomenon, is the altered expression associated with specific genetic polymorphisms, or minor sequence variations, in the HBD-1 gene specifically?

The researchers found that the OSCC cell lines had significantly lower baseline expression levels of HBD-1 and HBD-2 compared to the normal cell lines. They also determined that, when induced with stimuli, the OSCC cell lines were less adept at producing all three β-defensins. When the scientists drilled down to the sequence level, they noted four polymorphisms in the HBD-1 gene that were differentially distributed between the cancer and normal cells. They also found evidence that the reduced gene expression of HBD-1 was accompanied by altered HBD-1 allele frequencies in carcinoma cell lines, suggesting that this gene underwent loss of heterozygosity, a biological phenomenon characterized by the loss of one of the two alleles of a gene. “Our study and others present strong evidence of an association between β-defensin and oral cancer . . . ,” the researchers concluded. “Future genetic analysis of the β-defensin gene cluster with complete characterization of SNPs [polymorphisms] and gene copy number will be important in determining if these genetic markers may serve as diagnostic tools in screening individuals for risk of OSCC.”

  • Joly S, Compton LM, Pujol C, Kurago ZB, Guthmiller JM, "Loss of human β-defensin 1, 2, and 3 expression in oral squamous cell carcinoma,” Oral Microbiol Immunol 2009: 24:353-360. 




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This page last updated: February 26, 2014