title: Candida albicans increases tumor cell adhesion to endothelial cells in vitro: intraspecific differences and importance of the mannose receptor.
abstract: 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.
authors.affiliation: Department of Immunology, Faculty of Science and Technology, University of the Basque Country, UPV/EHU, Leioa, Spain. andoni.ramirez@ehu.es
authors.forename: Andoni
authors.initials: A
authors.lastname: Ramirez-Garcia
authors.forename: Beatriz
authors.initials: B
authors.lastname: Arteta
authors.forename: Ana
authors.initials: A
authors.lastname: Abad-Diaz-de-Cerio
authors.forename: Aize
authors.initials: A
authors.lastname: Pellon
authors.forename: Aitziber
authors.initials: A
authors.lastname: Antoran
authors.forename: Joana
authors.initials: J
authors.lastname: Marquez
authors.forename: Aitor
authors.initials: A
authors.lastname: Rementeria
authors.forename: Fernando L
authors.initials: FL
authors.lastname: Hernando
mesh_terms: D000818:Animals; D002176:Candida albicans / Q000378:metabolism*; D002177:Candidiasis / Q000378:metabolism / Q000382:microbiology*; D002448:Cell Adhesion; D002469:Cell Separation; D004727:Endothelium / Q000378:metabolism; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D007249:Inflammation; D020382:Interleukin-18 / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism*; D008546:Melanoma, Experimental; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis; D011956:Receptors, Cell Surface / Q000378:metabolism*
chemical_list: D020382:Interleukin-18; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface