Several years ago, a team of National Institute of Dental and Craniofacial Research (NIDCR)-supported scientists discovered that when pathogens challenged oral keratinocytes, cells that form the lining of the mouth and its soft tissues, these cells produce a variety of short antimicrobial peptides called β-defensins. The β-defensins were differentially expressed when exposed to different immune signaling molecules, implying that not all β-defensin responses are the same. These peptides serve as the keratinocyte’s first line of defense and signal nearby white blood cells to attack an invading pathogen. Defensins arise from 28 putative DNA coding regions that could be variably transcribed to suit the cell’s immediate needs. This heterogeneity suggests that different phenotypic profiles exist that may affect an individual’s susceptibility or resistance to disease. Further, cultured oral squamous cell carcinoma cells (OSCC), which stem from normal oral keratinocytes, variably expressed a β-defensin gene called HBD-1. In the journal Oral Microbiology and Immunology, the researchers take their discovery an intriguing step further. The group collected 19 recognized OSCC cell lines, established their own normal keratinocyte cell lines from the gingiva of healthy volunteers, and asked 2 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. When induced with stimuli, the OSCC cell lines were less adept at producing all 3 β-defensins. At the sequence level, they noted 4 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 2 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 will be important in determining if these genetic markers may serve as diagnostic tools in screening individuals for risk of OSCC. This original study by Joly S, et al, entitled “Loss of Human β-Defensin 1, 2, and 3 Expression in Oral Squamous Cell Carcinoma,” appeared in Oral Microbiology and Immunology.
(October 2009, Volume 24). (Source: NIDCR, Science News in Brief, September 24, 2009.)
