Characterization of the glycophenotype of human renal carcinomas Potential biomarkers of human renal carcinomas based on the glycophenotype of tumor cells, surrounding parenchyma and immune cell infiltrate

EVANGELINA ALMADA; CAROLINA I. DOMAICA; XIMENA LUCÍA RAFFO IRAOLAGOITIA; RAÚL GERMÁN SPALLANZANI; ANDREA ZIBLAT; FERNANDO SECIN; AGUSTIN ROVEGNO; GABRIEL ADRIÁN RABINOVICH; NORBERTO WALTER ZWIRNER

Congreso; LXII Reunion Anual de la Sociedad Argentina de Inmunologia; 2014

Renal cell carcinoma (RCC) is the most important type of adult renal epithelial neoplasm, accounting for 90% of all renal malignancies and that shows high mortality. RCC is unresponsive to traditional chemotherapies, highly radiation resistant, and lacks the genetic hallmarks of solid tumors. Also, no specific molecular prognostic marker has been recommended for routine clinical use. Carbohydrate expression pattern (glycophenotype) changes play crucial roles in carcinogenesis in other cancer types such as breast cancer, and the glycophenotype of the cell may confer susceptibility to immunoregulatory effects of galectins. Therefore, the aim of this work was to analyze the glycophenotype of RCC, surrounding tissue (parenchyma, P) and the immune cell infiltrate (ICI, CD45+ cells) using 10 samples from nephrectomies of human patients. By lectin binding assay (binding of biotinylated MAL-II, PNA, LEL, PHA-L and SNA lectins, detection with Streptavinin-PE and flow cytometry analysis) and expression clustering with Genesis we observed that 1) the glycophenotype of RCC, P and ICI was quite different; 2) RCC displayed low binding of SNA and high binding of MAL II, indicating that sialic acid is mostly displayed in a2,3 and not in a2,6 position, which is associated with poor prognosis in other cancer types; 3) RCC and ICI showed high binding of LEL, suggesting the existence of high poly-Lac-NAc repeats with potential galectin-1 binding sites; 4) PHA-L and PNA binding were mostly detected in ICI, indicating that complex N-glycans (branching) core-2-O-glycans are mainly associated with ICI. Therefore, the differential glycophenotype of tumor cells (LEL+PHA-L-SNA-), surrounding parenchyma (LEL-PHA-L-SNA-) and ICI (LEL+PHA-L+SNA+) may constitute useful biomarkers to distinguish between these cells. Also, such differential glycophenotype may determine the susceptibility to galectin-driven regulatory circuits and influence cancer immunoediting.