title: Patterns of Vasculature in Mouse Models of Lung Cancer Are Dependent on Location.
abstract: 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.
authors.affiliation: Department of Radiation Oncology, Molecular Imaging Program at Stanford and Bio-X Program, Stanford University, Stanford, CA, USA.
authors.forename: Marta
authors.initials: M
authors.lastname: Vilalta
authors.affiliation: Department of Radiation Oncology, Molecular Imaging Program at Stanford and Bio-X Program, Stanford University, Stanford, CA, USA.
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Hughes
authors.affiliation: Department of Radiation Oncology, Molecular Imaging Program at Stanford and Bio-X Program, Stanford University, Stanford, CA, USA.
authors.forename: Rie
authors.initials: R
authors.lastname: Von Eyben
authors.affiliation: Department of Radiation Oncology, Molecular Imaging Program at Stanford and Bio-X Program, Stanford University, Stanford, CA, USA.
authors.forename: Amato J
authors.initials: AJ
authors.lastname: Giaccia
authors.affiliation: Department of Radiation Oncology, Molecular Imaging Program at Stanford and Bio-X Program, Stanford University, Stanford, CA, USA. egraves@stanford.edu.
authors.forename: Edward E
authors.initials: EE
authors.lastname: Graves
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D008175:Lung Neoplasms / Q000098:blood supply* / Q000473:pathology*; D051379:Mice; D009368:Neoplasm Transplantation; D010477:Perfusion; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D012815:Signal Processing, Computer-Assisted; D040521:Subcutaneous Tissue
chemical_list: C495971:Hras protein, mouse; D016283:Proto-Oncogene Proteins p21(ras)
keywords: Non-invasive imaging in animal models; Preclinical models of cancer; Tumor microenvironment; Vasculature; Xenograft models