HUMAN RENAL ADIPOSE TISSUE FROM NORMAL AND TUMORAL KIDNEY REGULATES THE BEHAVIOR OF RENAL EPITHELIAL CELLS

CONTADOR, DAVID; SASSO, CORINA V.; CARÓN, RUBÉN W.; CAMPO-VERDE-ARBOCCO, FIORELLA; GÓMEZ, SILVINA E; ROMEO, LEONARDO R; ZYLA, LEILA E; SANTIANO, FLAVIA E.; PISTONE CREYDT, VIRGINIA; LOPEZ-FONTANA CM

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

Abstract: Tumor stroma is one of the emerging topicsof interest in cancer research. In the present work, we evaluated the effectsof Conditioned Media (CMs) of human adipose tissue explants from normal (hRAN)and tumor (hRAT) kidney on proliferation of tumor (786-O, ACHN) and non tumor(NK-2) renal epithelial cells. We also evaluated: 1) leptin, adiponectin andversican mRNA expression in hRAN and hRAT; 2) adiponectin, ADAMTS1 andperilipin expression in hRAN- and hRAT-CMs; and 3) adiponectin and perilipinexpression in hRAN- and hRAT.Humanrenal adipose tissues were obtained from patients with renal cell carcinoma(hRAT, n=6) and kidney donors (hRAN, n=8). The CMs from hRAN and hRAT werecollected after 24h of incubation. 786-O, ACHN and NK-2 cells were grown andincubated with CMs for 24 and 48h. Proliferation was quantified by MTT; mRNAexpression was evaluated by real-time PCR, protein expression by WB andimmunohistochemistry. Statistical differences between experimental conditionswere evaluated by one-way ANOVA or t test. Tukey´s post hoc tests wereperformed.We founda higher RNA expression of leptin (a major adipokine with tumorigenic effects)and versican (a proteoglycan that is essential in epithelial-stromalinteraction and intracellular signaling) in hRAT vs. hRAN explants (p<0.01). Also, we observed that adiponectin(a major adipokine with anti-tumorigenic effects), and perilipin expressionwere significantly increased in hRAN vs.hRAT explants (p<0.05) and in addition we observed alower protein expression of perilipin (marker for mature differentiatedadipocyte) in hRAT-CMs vs. hRAN-CMs(p<0.05). Added to this, hRAN-CMs significantly increased the proliferationof 786-O and HK-2 compared to control- and hRAT-CMs after 24h (p<0.05). Inconclusion, the changes observed in the adipose microenvironment could befavoring tumor progression and therefore, the tumor stroma should be taken intoconsideration when dealing with a malignancy.