INVESTIGADORES
ZWIRNER Norberto Walter
congresos y reuniones científicas
Título:
Glycophenotype as potential biomarker of tumor cells, surrounding parenchyma and immune cell infiltrate in human renal carcinomas
Autor/es:
ALMADA, EVANGELINA; DOMAICA, CAROLINA INÉS; RAFFO IRAOLAGOITÍA, XIMENA LUCÍA; SPALLANZANI, RAÚL GERMÁN; ZIBLAT, ANDREA; SECÍN, FERNANDO; ROVEGNO, AGUSTÍN; RABINOVICH, GABRIEL ADRIÁN; ZWIRNER, NORBERTO WALTER
Lugar:
Mar del Plata
Reunión:
Congreso; 62a Reunión Anual de la Sociedad Argentina de Inmunología; 2014
Institución organizadora:
Sociedad Argentina de Inmunología
Resumen:
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.