title: Phosphorescence-assisted microvascular O(2) measurements reveal alterations of oxygen demand in human metastatic colon cancer in the liver of superimmunodeficient NOG mice.
abstract: 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 O(2) 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 PO(2) 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 O(2) consumption, suggesting that the tumor O(2) consumption is smaller than that in the residual liver. At 2 weeks, portal PO(2) was significantly smaller than controls, while the central PO(2) was not comparably decreased, indicating that metastatic foci increased the O(2) 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.
authors.affiliation: Department of Surgery, School of Medicine, Keio University, Tokyo 160-8582, Japan.
authors.forename: Kan
authors.initials: K
authors.lastname: Handa
authors.forename: Mitsuyo
authors.initials: M
authors.lastname: Ohmura
authors.forename: Chiyoko
authors.initials: C
authors.lastname: Nishime
authors.forename: Takako
authors.initials: T
authors.lastname: Hishiki
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Nagahata
authors.forename: Kenji
authors.initials: K
authors.lastname: Kawai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suemizu
authors.forename: Masato
authors.initials: M
authors.lastname: Nakamura
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Wakui
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kitagawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Suematsu
authors.forename: Kosuke
authors.initials: K
authors.lastname: Tsukada
mesh_terms: D000818:Animals; D003110:Colonic Neoplasms / Q000473:pathology*; D045325:HCT116 Cells; D006801:Humans; D016867:Immunocompromised Host / Q000502:physiology*; D008113:Liver Neoplasms / Q000098:blood supply* / Q000473:pathology / Q000503:physiopathology / Q000556:secondary*; D008163:Luminescent Measurements / Q000379:methods*; D051379:Mice; D055806:Microvessels / Q000503:physiopathology*; D010100:Oxygen / Q000378:metabolism*; D010313:Partial Pressure; D014699:Venules / Q000503:physiopathology
chemical_list: D010100:Oxygen