Tumor hypoxia develops due to uncontrollable cell proliferation, altered metabolism, and abnormal tumor blood vessels resulting in reduced transport of oxygen and nutrients to the tumor and its microenvironment. It is one of the main features of solid tumors and was shown to correlate with poor prognosis of cancer patients. Using optically-enabled intravital imaging techniques in transparent window chamber animal models, my research aims to develop a better understanding of tumor hypoxia and methods of measuring it to help to predict patients’ outcome as well as identify patients who could benefit from hypoxia-targeted treatments. My translationally-driven projects are looking at both pancreatic cancer (funded by the Terry Fox Research Institute), a cancer with a very low survival rate, and acute myeloid leukemia, a blood-born cancer we don’t know much about when it comes to hypoxia (funded by the Leukemia & Lymphoma Society of Canada).
We have transfected pancreatic cancer cells and acute myeloid leukemia cancer cells to express mCherry only (red, top) or mCherry and GFP, driven by a hypoxia-response element (HRE, green, bottom). Representative fluorescent and differential interference contrast images show that there is a low level of GFP positive cells under normoxic conditions, while almost all cells become GFP positive under hypoxic conditions. Cells were incubated under normoxic or hypoxic (1% O2) conditions for 24h prior to imaging and GFP/mCherry ratio was measured to indicate the proportion of hypoxic cells (bar chart).