Abstract
Candida leukoplakia (OLK) is a kind of oral leukoplakia combined with chronic candidal infection, which plays an important role in the malignant transformation of OLK. However, little is known about the etiology, including susceptibility of leukoplakia to candidal adhesion, invasion and infection. Some antimicrobial peptides secreted by oral epithelial cells or fibroblasts potentially have antifungal activities against Candida albicans (C. albicans). In this study, we established three co-culture models to simulate different C. albicans-fibroblasts interactions during progression of candida leukoplakia. The susceptibility of oral leukoplakia-associated fibroblasts (LKAFs) to C. albicans and its underlying mechanism were determined. Samples of 14 LKAFs and 10 normal fibroblasts (NFs) were collected. The co-culture models showed that LKAFs had promoted the adhesion, invasion, and survival of C. albicans compared with NFs. CX3CL1, a chemokine with antifungal activity, was less abundant in LKAFs than NFs. Overexpression of CX3CL1 via transfection in LKAFs could partly restore the resistance to C. albicans. We also showed that inhibition of ERK could suppress CX3CL1 secretion. While phosphor-ERK was inhibited in LKAFs compared with NFs. Besides, the mRNA expression of a shedding enzyme for CX3CL1, disintegrin and metalloproteinase domain (ADAM) 17 was decreased in LKAFs than NFs. In conclusion, LKAFs produced and secreted less CX3CL1 by inhibiting the ERK signaling pathway, thereby contributing to impaired cell resistance to C. albicans.
Highlights
Oral leukoplakia (OLK) is one of the most common potentially malignant oral disorders
It is in agreement that cancer activates resident fibroblasts, termed carcinoma-associated fibroblasts, which participate in neoplastic progression (Mao et al, 2013). α-smooth muscle actin (α-SMA) and fibroblast activation protein (FAP) are well-established markers of CAFs (Kalluri and Zeisberg, 2006)
The results showed that leukoplakia-associated fibroblasts (LKAFs) exhibited weak and moderate positive staining for α-SMA and FAP, whereas CAFs had strong positive staining (Figure 1A)
Summary
Oral leukoplakia (OLK) is one of the most common potentially malignant oral disorders. The term “candida leukoplakia” is used to describe leukoplakia combined with chronic candidal infection, which plays an important role in the malignant transformation of OLK (Lehner, 1964). C. albicans is the most common Candida species in the oral cavity where it is a commensal fungus in healthy individuals (Odds, 1988). Systemic factors such as severe nutritional deficiency and generalized immune suppression play contributory roles in candidal infections. The occurrence of these systemic disorders is not very high in cases of candida leukoplakia (Sitheeque and Samaranayake, 2003). Epithelial disorders in OLK, such as atrophy, hyperplasia, and dysplasia, may compromise the mucosal barrier and facilitate candida invasion as well (Samaranayake, 1990)
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