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Patterns of Vasculature in Mouse Models of Lung Cancer Are Dependent on Location

Abstract

Purpose

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.

Procedures

To compare the presence and functionality of vessels in these tumor models, we studied vascular perfusion in vivo in real time.

Results

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.

Conclusions

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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Acknowledgments

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.

Author information

Correspondence to Edward E. Graves.

Ethics declarations

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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Cite this article

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

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Key words

  • Preclinical models of cancer
  • Xenograft models
  • Non-invasive imaging in animal models
  • Tumor microenvironment
  • Vasculature