Candida albicans Enhances the Progression of Oral Squamous Cell Carcinoma In Vitro and In Vivo

• Published in: mBio Vol. 13; no. 1; p. e0314421
• Main Authors: Vadovics, Máté, Ho, Jemima, Igaz, Nóra, Alföldi, Róbert, Rakk, Dávid, Veres, Éva, Szücs, Balázs, Horváth, Márton, Tóth, Renáta, Szücs, Attila, Csibi, Andrea, Horváth, Péter, Tiszlavicz, László, Vágvölgyi, Csaba, Nosanchuk, Joshua D, Szekeres, András, Kiricsi, Mónika, Henley-Smith, Rhonda, Moyes, David L, Thavaraj, Selvam, Brown, Rhys, Puskás, László G, Naglik, Julian R, Gácser, Attila
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 01-02-2022
• Subjects: Animals; cancer; Candida albicans; Candida albicans - genetics; Candidiasis, Oral; Carcinogenesis - genetics; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Host-Microbial Interactions; Humans; Mice; Mouth Neoplasms - genetics; Mouth Neoplasms - metabolism; Mouth Neoplasms - pathology; oral squamous cell carcinoma; progression; Research Article; Squamous Cell Carcinoma of Head and Neck; Candida albicans; progression; cancer; oral squamous cell carcinoma
• ISSN: 2150-7511; 2150-7511
• DOI: 10.1128/mBio.03144-21

Oral squamous cell carcinoma (OSCC) is associated with oral Candida albicans infection, although it is unclear whether the fungus promotes the genesis and progression of OSCC or whether cancer facilitates fungal growth. In this study, we investigated whether C. albicans can potentiate OSCC tumor development and progression.
, the presence of live C. albicans, but not Candida parapsilosis, enhanced the progression of OSCC by stimulating the production of matrix metalloproteinases, oncometabolites, protumor signaling pathways, and overexpression of prognostic marker genes associated with metastatic events. C. albicans also upregulated oncogenes in nonmalignant cells. Using a newly established xenograft
mouse model to investigate OSCC-C. albicans interactions, oral candidiasis enhanced the progression of OSCC through inflammation and induced the overexpression of metastatic genes and significant changes in markers of the epithelial-mesenchymal transition. Finally, using the 4-nitroquinoline 1-oxide (4NQO) murine model, we directly correlate these
and short-term
findings with the progression of oncogenesis over the long term. Taken together, these data indicate that C. albicans upregulates oncogenes, potentiates a premalignant phenotype, and is involved in early and late stages of malignant promotion and progression of oral cancer.
Oral squamous cell carcinoma (OSCC) is a serious health issue worldwide that accounts for 2% to 4% of all cancer cases. Previous studies have revealed a higher yeast carriage and diversity in oral cancer patients than in healthy individuals. Furthermore, fungal colonization in the oral cavity bearing OSCC is higher on the neoplastic epithelial surface than on adjacent healthy surfaces, indicating a positive association between oral yeast carriage and epithelial carcinoma. In addition to this, there is strong evidence supporting the idea that
contributes to carcinogenesis events in the oral cavity. Here, we show that an increase in Candida albicans burden promotes an oncogenic phenotype in the oral cavity.