Adaptation to an acid microenvironment promotes pancreatic cancer organoid growth and drug resistance [acid]

We investigated transcriptomic changes in pancreatic ductal organoids under adaptation to an acidic extracellular environment. Overall design: Wild type ("mN10"), KrasG12D ("mP4"), p53 knockout ("mP4 p53KO"), and Trp53R273H ("mP4 p53R273H") organoids were gradually acid adapted from pH 7.4 to pH 6.7 ("AA") by decreasing pH of their culture medium by approximately ?=0.125 pH every week for nine weeks. After reaching the desired pH of 6.7, the organoids were cultured for 2 weeks (week 8-9) at pH 6.7. Then, acid adapted organoids were split into two fractions: i) cultured at pH 6.7 until week 11, and ii) cultured at their physiological pH of 7.4 until week 11 ("AA->pH7.4").