title: High interstitial fluid pressure is associated with tumor-line specific vascular abnormalities in human melanoma xenografts.
abstract: OBJECTIVE
  Interstitial fluid pressure (IFP) is highly elevated in many solid tumors. High IFP has been associated with low radiocurability and high metastatic frequency in human melanoma xenografts and with poor survival after radiation therapy in cervical cancer patients. Abnormalities in tumor vascular networks have been identified as an important cause of elevated tumor IFP. The aim of this study was to investigate the relationship between tumor IFP and the functional and morphological properties of tumor vascular networks.
  
  
  METHODS
  A-07-GFP and R-18-GFP human melanomas growing in dorsal window chambers in BALB/c nu/nu mice were used as preclinical tumor models. Functional and morphological parameters of the vascular network were assessed from first-pass imaging movies and vascular maps recorded after intravenous bolus injection of 155-kDa tetramethylrhodamine isothiocyanate-labeled dextran. IFP was measured in the center of the tumors using a Millar catheter. Angiogenic profiles of A-07-GFP and R-18-GFP cells were obtained with a quantitative PCR array.
  
  
  RESULTS
  High IFP was associated with low growth rate and low vascular density in A-07-GFP tumors, and with high growth rate and high vascular density in R-18-GFP tumors. A-07-GFP tumors showed chaotic and highly disorganized vascular networks, while R-18-GFP tumors showed more organized vascular networks with supplying arterioles in the tumor center and draining venules in the tumor periphery. Furthermore, A-07-GFP and R-18-GFP cells differed substantially in angiogenic profiles. A-07-GFP tumors with high IFP showed high geometric resistance to blood flow due to high vessel tortuosity. R-18-GFP tumors with high IFP showed high geometric resistance to blood flow due to a large number of narrow tumor capillaries.
  
  
  CONCLUSIONS
  High IFP in A-07-GFP and R-18-GFP human melanoma xenografts was primarily a consequence of high blood flow resistance caused by tumor-line specific vascular abnormalities.
authors: Group of Radiation Biology and Tumor Physiology, Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway. Trude.Golimo.Simonsen@rr-research.no
authors: Trude G
authors: TG
authors: Simonsen
authors: Jon-Vidar
authors: JV
authors: Gaustad
authors: Marit N
authors: MN
authors: Leinaas
authors: Einar K
authors: EK
authors: Rofstad
mesh_terms: D000818:Animals; D001160:Arterioles / Q000002:abnormalities / Q000473:pathology / Q000503:physiopathology; D001808:Blood Vessels / Q000002:abnormalities* / Q000473:pathology / Q000503:physiopathology*; D045744:Cell Line, Tumor; D045604:Extracellular Fluid / Q000502:physiology*; D005260:Female; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D008545:Melanoma / Q000097:blood / Q000098:blood supply* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic / Q000473:pathology; D011312:Pressure; D012039:Regional Blood Flow; D012878:Skin Neoplasms / Q000097:blood / Q000098:blood supply* / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors; D014699:Venules / Q000002:abnormalities / Q000473:pathology / Q000503:physiopathology; D023041:Xenograft Model Antitumor Assays
chemical_list: D049452:Green Fluorescent Proteins