Abstract 456: Adaptation of cancer cells to hypoxic environments for tumor progression

There have been a number of reports mentioning the significance of adaptation of cancer cells to hypoxic environments in tumor growth, invasion, and metastases. However, understanding of molecular aspects based on in vivo evidence still remains insufficient. We established an in vivo tumor progression model by transfer of human colorectal cancer HCT116 cells cultured under hypoxia to NOD/Shi-scid, IL-2Rγnull (NOG) mouse recipients. The hypoxic culture resulted in invasive proliferation of subcutaneous tumors. Immnohistochemical staining for molecular markers, such as E-cadherin, vimentin and BCRP1, demonstrated that adaptation of HCT116 cells to hypoxia was associated with increased frequencies of epithelial-mesenchymal transition and cancer stem cell-like appearance. To investigate the molecular basis of such effects of hypoxia on tumor progression, biological and molecular profiles of HCT116 cultured under hypoxia were analyzed. The hypoxic culture resulted in slowing cell cycling and increase in the side population cell frequency, suggesting induction of stemness. Capillary electrophoresis-mass spectrometric analysis revealed altered metabolism in hypoxic HCT116 cells, which appeared to be associated with adaptation to hypoxia. Gene expression profiling of the cultured cells under pharmacological inhibition of p53, which is not mutated in HCT116 cells, presented evidence for dependence of the adaptation to chronic mild but not acute severe hypoxia on p53 function. Our results provided insights into molecular basis of tumor progression critically directed by hypoxia. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 456.