Cells derived from renal proximal epithelia are affected by extracellular pH in a different way than cells derived from clear renal cell carcinoma: Effect of NHE1.

DI GIUSTO, GISELA; NATALIA BELTRAMONE; RIVAROLA, VALERIA; PORTA MICAELA; FORD, PAULA; MAZZOCCHI MARINA; PIZZONI, ALEJANDRO; CAPURRO, CLAUDIA

Mar del Plata

Congreso; Reunión Anual de la Sociedad Argentina de Investigación Clínica, LXVI Reunión Anual de la sociedad Argentina de Inmunología y Reunión Anual de la Sociedad Argentina de Fisiología.; 2018

The association between cell death and intracellular pH elicits the possibility that extracellular pH (pHe) may modify cell survival. Moreover, as tumor extracellular acidity is a hallmark of cancers, is probable that pHe affects differently cancer or normal cells. The aim of this study was to investigate whether exposure to acidic or alkaline media altered cell survival in two renal cell models: HK2, derived from normal human proximal epithelial cells and 786-O, derived from human renal clear cell carcinoma. Cells were exposed for 24h to media with different pHe and then cell survival was estimated by acrydin orange?ethidium bromide experiments. Our results show that HK2 cell survival decays with an acidification of 0.1 pH units (∆ Cell death at pH 7.3 = 14.30 ± 3.00, p< 0.05 n=5) while 786-O cells can survive even at pH 6.4 (∆ Cell death at pH 6.4 = 0.24 ± 0,50 ns n=5). On the other hand 786-O cells were more sensible to alkalinization than HK2 cells. While an alkalinization of 0.1 affected only malignant cells (∆ Cell death at pH 7.5 HK2= 0.03 ± 0.50 vs 786-O= 10.57 ± 2.00 p< 0.01 n=10) higher alkalinization affected both cell lines. As control of pHi is regulated in part by the isoform 1 of Na/H exchanger (NHE1) we inhibited the transporter at different pHe. At pH=7.4 cell death is greater in both cell lines. However at pH=7.5 cell death rises in normal cells and drops in malignant ones (NHE1 Cell death HK2= 16 ± 1 vs 786-O= -9 ± 2 p< 0.01 n=12). Thus, NHE1 regulation is altered in malignant cells. In summary while tumor acidification might allow normal tissue destruction and tumor overgrowth, countering the tumor acidification with mild alkalosis might improve tumor control without normal tissue damage.