The dimorphic fungus Candida albicans is able to trigger a
cytokine-mediated pro-inflammatory response that increases
tumor cell adhesion to hepatic endothelium and
metastasis. To check the intraspecific differences in this effect, we used an in vitro murine model of hepatic response against C. albicans, which made clear that
tumor cells adhered more to endothelium incubated with blastoconidia, both live and killed, than germ tubes. This finding was related to the higher
carbohydrate/
protein ratio found in blastoconidia. In fact, destruction of
mannose ligand residues on the cell surface by
metaperiodate treatment significantly reduced
tumor cell adhesion induced. Moreover, we also noticed that the effect of clinical strains was greater than that of the reference one. This finding could not be explained by the
carbohydrate/
protein data, but to explain these differences between strains, we analyzed the expression level of ten genes (ADH1, APE3, IDH2, ENO1, FBA1, ILV5, PDI1, PGK1, QCR2 and TUF1) that code for the
proteins identified previously in a mannoprotein-enriched pro-metastatic fraction of C. albicans. The results corroborated that their expression was higher in clinical strains than the reference one. To confirm the importance of the mannoprotein fraction, we also demonstrate that blocking the
mannose receptor decreases the effect of C. albicans and its
mannoproteins, inhibiting
IL-18 synthesis and
tumor cell adhesion increase by around 60%. These findings could be the first step towards a new treatment for solid organ
cancers based on the role of the
mannose receptor in C. albicans-induced
tumor progression and
metastasis.