CELLS DERIVED FROM CLEAR RENAL CELL CARCINOMA CAN SURVIVE BETTER THAN CELLS DERIVED FROM RENAL PROXIMAL EPITHELIA TO EXTRACELLULAR ACIDOSIS

VAN BALEN V; MECHALI A; AMABILE MN; BELTRAMONE N; CAPURRO C; DI GIUSTO G; FORD P; RIVAROLA V

Mar del Plata

Congreso; Reunion Conjunta SAIC SAI SAFIS; 2022

Sociedad Argentina de Fisiologia

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, pHe may affect in a different way cancer and normal cells. This study aimed to investigate whether exposure to acidic 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 (RCC). We evaluate the effect of acidosis at different exposure times (24-72h) and different HCl concentrations. The percentage of cell death was evaluated with acridine orange?ethidium bromide dyeing followed by fluorescent microscopy. Our results showed that while 786-O cell survival was not affected by up to 72h of 9.6mM HCl exposure (%Cell death, control: 8.1 ± 1.0 vs. 72h Acid: 7.8 ± 1.7, ns n=60), HK2 cell survival decays with even 24hs of this acidification (%Cell death, control: 8.1 ± 0.8 vs. 24h Acid: 24.9 ± 4.4, p< 0.01 n=70). While 786-O cells were even able to resist 72h exposure to 19.2 mM HCl, HK2 cells were not able to survive that acidification (%Cell death with 72h 19.2 mM HCl, HK2= 80.0 ± 2.0, p< 0.001 n=5 vs. control HK2 cells; 786-O = 9.0 ± 1.0 ns n=5 vs. control 786-O cells). These results show that RCC cells adapt to an acidic environment. To test the hypothesis that the NHE1 isoform of the Na+/H+ exchanger could be involved in this acidic adaptation, we inhibited NHE1. NHE1 inhibition (-NHE) rise 786-O cell death (%Cell death after 24h with 9.6mM HCl, +NHE1: 8.0 ± 1.2 vs. -NHE1: 13.8 ± 2.5, p< 0.05 n=15). In conclusion, RCC cell adaptation to acidosis depends on the NHE1 function. Further studies are needed to assess the mechanism of this adaptation.