BioProject

Many solid tumors grow slowly, with an average volume doubling time of several months to multiple years. More...

Many solid tumors grow slowly, with an average volume doubling time of several months to multiple years. Yet, most studies to date have focused mainly on the short-term fate of cancerous cells upon exposure to acidic pHe (extracellular pH), a common hallmark of tumor microenvironment. Little is known about how solid tumors, such as intractable PDAC originated from pancreatic ductal cells that secrete alkaline fluids, evolve to tolerate and adapt to the sustained and prolonged exposure of acidic pHe stress. We established a series of PDAC tumor cells exposed to prolonged periods of extracellular acidification. These biological materials were further subjected to microarray analysis to detail the genome-wide gene expression profiles and to identify the differential expressed genes related to the long-term adaptation of PDAC tumor cells to the extracellular chronic acidosis stress. Overall design: A total of six groups in duplicates were established, including 1) control group (Ctrl), in which SUIT-2 cells were grown in control medium at physiological pHe 7.4; 2-3) two buffered group, in which tumor cells were incubated in control medium supplemented with non-volatile HEPES/PIPES buffer at pHe 7.4 for either a short period of 2-3 weeks (Buff_2W) or a long period of 10-12 months (Buff_12M); and 4-6) three acidic stress-treated groups, in which PDAC cells were cultured in control medium buffered with HEPES/PIPES at pHe 6.7 for either a short period of 2-3 weeks to reflect the initial stage of extracellular acidification (denoted hereafter as SA for short-term acidic exposure); a medium period of 4-5 months to mirror the previously reported median TVDT in pancreatic cancer patients (denoted hereafter as MA for mid-term acidic exposure); or a long period of 10-12 months to simulate the prolonged TVDT in early cancer patients with small localized tumors (denoted hereafter as LA for long-term acidic exposure). Less...