CLUSTERIN PRESENT ON HUMAN BREAST CANCER BEARS DC-SIGN BINDING FUCOSYLATED GLYCANS

CARREGAL, SOL; SEDLIK, CHRISTINE; PIAGGIO, ELIANE; LOPEZ MALIZZIA, ALVARO; CEBALLOS, ANA; AMIGORENA, SEBASTIAN; MERLOTTI IPPÓLITO, ANTONELLA; VARESE, AUGUSTO; GEFFNER, JORGE; SABATTE, JUAN

Mar del Plata

Congreso; SAIC SAI SAFE 2016; 2016

Sociedad Argentina de Inmunología

Clusterin (CLU) is a ubiquitous glycoprotein with extracellular chaperone activity. We have previously shown that clusterin isolated from human seminal plasma bears a set of glycans rich in fucose with high affinity for DC-SIGN present on dendritic cells (DCs); it targets misfolded proteins to DC-SIGN promoting their endocytosis and degradation; and that semen clusterin treated DCs promotes expansion of CD4+CD25+FOXP3+ T-cells. On the other hand, numerous studies have shown that glycosylation changes are associated with the development of cancer and CLU overexpression has been reported in different tumors types. Furthermore, DC-SIGN ligands impose different functional profiles on DCs depending on their glycosylation pattern. Hence, we hypothesize that tumor-CLU has a similar glycosylation pattern and properties of seminal CLU.The presence and properties of CLU were analyzed on human luminal breast cancer samples, and non-invaded breast tissue was used as control. The concentration of total CLU showed no significant differences between tumor and ?healthy? tissues (n=20, p=0.3890). The presence of fucose motifs on clustrein was analyzed by ELISA using the fucose binding lectin Lotus tetragonolobus. The presence of fucose motifs was higher on tumor-CLU than helthy-tissue CLU (n=14 p=0.004). Moreover, tumor-CLU binds to DC-SIGN when analyzed by western-blot while CLU from healthy tissue does not (n=5). Finally, we observed that CLU strongly co-localize with Lewis X type fucose motifs on the breast cancer cell line MCF7 and on primary breast cancer cells (n=3). These results showed that breast tumor-CLU bears fucosylated glycans and binds o DC-SIGN. Ongoing experiments will confirm whether tumor-CLU also has chaperone activity and promotes expansion of CD4+CD25+FOXP3+ T-cells, acting as a new mediator of tumor immune-evasion.