Preclinical studies of hypoxia are generally done using ectopic xenograft tumors, which behave differently from human tumors. Our previous findings have shown that subcutaneously implanted lung tumors exhibit more hypoxia than their orthotopic implanted or spontaneous K-ras-induced counterparts. We hypothesize that differences in hypoxia are due to site-specific differences in vascularity and perfusion.
To compare the presence and functionality of vessels in these tumor models, we studied vascular perfusion in vivo in real time.
Orthotopically implanted and spontaneous K-ras-induced lung tumors showed elevated perfusion, demonstrating vasculature functionality. Little contrast agent uptake was observed within the subcutaneously implanted tumors, indicating vascular dysfunction. These findings were corroborated at the microscopic level with Hoechst 33342 and Meca-32 staining.
From these observations, we concluded that differences in hypoxia in experimental models is related to vessel perfusion. Thus, appropriate selection of preclinical lung tumor models is essential for the study of hypoxia, angiogenesis and therapies targeting these phenomena.
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We acknowledge Dr. Alejandro Sweet-Cordero for the donation of the spontaneous lung cancer mouse model and the assistance of Leanne Sayles with the mouse model. The funding for this study was provided by NCI R01 CA131199, NCI P01 CA067166, and Agència de Gestió d’Ajuts Universitaris i de Recerca, Generalitat de Catalunya.
All animal experiments were done according to a protocol approved by the Institutional Animal Care and Use Committee.
Conflict of Interest
The authors declare that they have no conflict of interest.
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Vilalta, M., Hughes, N.P., Von Eyben, R. et al. Patterns of Vasculature in Mouse Models of Lung Cancer Are Dependent on Location. Mol Imaging Biol 19, 215–224 (2017). https://doi.org/10.1007/s11307-016-1010-5
- Preclinical models of cancer
- Xenograft models
- Non-invasive imaging in animal models
- Tumor microenvironment