Abstract 993: Enhanced EGFR activity of prostate cancer cells by low pH, low glucose environment

Abstract

Abstract Background: Hypoxia, lack of nutrients and high aerobic glycolysis creates a microenvironment of high lactate, low glucose and low pH conditions within a solid tumor. The purpose of the current research is to study how the cancer cells adapt to a microenvironment with low pH, low glucose and high lactate levels with selective growth advantages. Methods: We simulated solid tumor microenvironment conditions by making DMEM media with low glucose (2mM), high lactate (10mM) and low pH (6.5). To study the growth advantages of this microenvironment, we determined the effect of low pH, low glucose and lactate medium on EGFR activation. Prostate cancer (PC3) cells were grown in six-well plates in 10% serum containing DMEM and serum starved overnight before they were changed to experimental medium. Control cells were grown in normal DMEM. We treated PC3 cells growing in normal DMEM and experimental medium with EGF at 1ng/ml. Protein samples were collected at different time intervals and subjected to western blotting to observe the activation of EGFR by using phospho EGFR antibody. EGFR and actin antibodies were used as control and loading controls, respectively. Results: Robust and sustained phosphorylation of EGFR for longer time was observed with EGF treatment when the cells were grown in low pH, low glucose and high lactate medium when compared with the cells grown in normal DMEM medium. Conclusion: The robust activation of EGFR with low pH, low glucose and high lactate medium suggest that the microenvironment containing high lactate provides growth or survival advantages to the cancer cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 993. doi:10.1158/1538-7445.AM2011-993