Phosphorescence-Assisted Microvascular O2 Measurements Reveal Alterations of Oxygen Demand in Human Metastatic Colon Cancer in the Liver of Superimmunodeficient NOG Mice
We aimed to examine metabolism of human cancer in vivo and utilized superimmunodeficient NOG mice as an experimental model of hepatic metastasis, where human colon cancer cell line HCT116 transfected with Venus, the mutant GFP was injected intrasplenically. The mice were pretreated with Pd-porphyrin to quantify local O2 tension through intravital phosphorescence assay. In this model, a majority of metastatic foci occurred in periportal regions but not in central regions. At 1 week after the transplantation, a PO2 drop in periportal regions was minimal without any notable decrease in microvascular blood flow. Under these conditions, there was a negative correlation between the size of metastatic foci and the lobular O2 consumption, suggesting that the tumor O2 consumption is smaller than that in the residual liver. At 2 weeks, portal PO2 was significantly smaller than controls, while the central PO2 was not comparably decreased, indicating that metastatic foci increased the O2 consumption, while the residual liver decreased it. These results suggest metastatic tumors derived from human colon cancer exhibit notable aerobic metabolism during their developmental process, compromising respiration of the rest of the tissue regenerated during tumor development.
KeywordsHepatic Lobule Metastatic Focus Severe Combine Immunodeficiency Human Colon Cancer Cell Line Microvascular Flow
This work was supported by RIKEN Supercomputing Science Grant by MEXT and by Grant-in-aid for Creative Scientific Research 17GS0419 from MEXT.