Impact of Candida albicans on β-Defensins expression in Oral Carcinoma

Human beta defensins (HBDs) are cationic antimicrobial peptides produced by epithelial cells in the oral cavity. Recently, we reported a β-defensin deficiency in oral cancer vs. normal cell lines (Compton et al., 2006). Additionally, it has been suggested that cancerous tissues have an increased susceptibility for Candida colonization and a reduced HBD-2 production in oral squamous cell carcinoma (OSCC) in response to C. albicans. Objectives: Our goal was to compare HBD-1, 2, and 3 expression in cancer and normal keratinocyte cell lines co-cultured with C. albicans as opposed to basal expression. Additionally, we examined the adhesion of Candida when co-cultured with normal and cancer cell lines. Methods: 2 human OSCC cell lines and 2 primary gingival keratinocyte control cell lines were co-cultured for 24 hours with 3 C. albicans strains (FC5, FC16, and FC20) at 10², 10⁴, and 10⁶ cells/ml. Total RNA was extracted and expression of HBDs were quantitatively assessed by Real-Time PCR. Adhesion was estimated as percentage of C. albicans cells attached to the monolayer compared to total number of cells (supernatant + monolayer). Results: Basal level of expression of the cell cultures for all three HBDs were significantly lower in cancer cell lines (P<0.05); HBD-2 expression was absent in the cancer lines. HBD-1 and 3 expression was significantly induced in SCC19 when co-cultured with C. albicans at 10⁴ cells/ml (P=0.001 and 0.0023 respectively). However, the amount of expression was still significantly less than basal expression observed for control cell lines (P=0.0037). C. albicans adhesion varied in function of the cell line but did not correlate with the strain, inoculum, or level of HBD expression. Conclusions: Our results suggest that cancer cell lines may display an altered defensin expression in response to co-infection with C. albicans. These results corroborate the hypothesis that microorganisms may influence cancer progression.