Absence of Host-Site Influence on Angiogenesis, Blood Flow, and Permeability in Transplanted RG-2 Gliomas

  1. Peter Molnar1,2,
  2. Istvan Fekete1,3,
  3. Kurt E. Schlageter1,4,
  4. Gregory D. Lapin1,5,6 and
  5. Dennis R. Groothuis1,6,7
  1. Department of Neurology, Northwestern University Medical School, Evanston Northwestern Healthcare, Evanston, Illinois

    Abstract

    The host site is believed to regulate tumor angiogenesis, which could result in site-dependent drug delivery parameters, greatly affecting experimental tumor research. In RG-2 rat gliomas we measured cellular proliferation; cell cycle time was the same for RG-2 cells in brain and s.c. tumors (25 h), and was the same for endothelial cells in these tumors (46 h). We measured the transcapillary transfer constant (K) of α-aminoisobutyric acid and blood flow (F) with iodoantipyrine in RG-2 gliomas transplanted into brain, liver, kidney, muscle, s.c. tissue, and into the abdominal cavity. Data was evaluated by quantitative autoradiography and direct tissue sampling. The variation of F (12.6–84.0 ml/g/min) andK (26.1–49.2 μl/g/min) in RG-2 tumors in the different host sites was less than in surrounding tumor-free tissue (F = 20–1500 ml/g/min and K = 1.6–700 μl/g/min). In contrast to other models, RG-2 does not result in tumors with host site-dependent behavior. The RG-2 tumor cells appear to participate in, if not dominate, the angiogenesis process regardless of the host site. Values of F andK were more dependent on tumor topography (center versus periphery) and local histological features (necrosis versus viable tumor) than host site. We believe that the methods used for data acquisition may introduce as much variability in Resultsas the tumors themselves and that to better understand how tumor angiogenesis affects the vascular phenotype, comparative studies are needed to validate the results obtained with newer methodologies.

    Footnotes

    • Send reprint requests to: Dr. Dennis R. Groothuis, Division of Neurology, Burch Hall, Evanston Hospital, 2650 Ridge Ave., Evanston, IL 60201. E-mail: drgroothuis{at}nwu.edu

    • ↵1 Present address: Department of Neurology, Northwestern University Medical School, Evanston Northwestern Healthcare, Evanston, IL 60201.

    • ↵2 Mark Moritz Visiting Scholar, Department of Neurology, Northwestern University Medical School, Evanston Northwestern Healthcare, Evanston, IL 60201. (Present address: Hungarian-Japanese Electron Microscopic Center (HJEMC), Department of Pathology, University Medical School of Debrecen, P.O. Box 23, H-4014 Debrecen, Hungary).

    • ↵3 Present address: Department of Neurology, University Medical School of Debrecen, P.O. Box 24, H-4012 Debrecen, Hungary.

    • ↵4 Present address: Department of Neurosurgery, National Institutes of Health, Bethesda, MD 20892.

    • ↵5 Present address: Department of Biomedical Engineering, Northwestern University, Evanston, IL 60201.

    • ↵6 Present address: Northwestern University Institute for Neuroscience, Northwestern University, Evanston, IL 60208.

    • ↵7 Present address: Department of Neurobiology and Physiology, Northwestern University, Evanston, IL 60208.

    • This work was supported by National Institutes of Health Grant R01-NS12745 and by the Richard M. Lilienfield Memorial Fund. P.M. was supported by the Mark Moritz Brain Tumor Research Fellowship and by the following grants: OTKA T020128; ETT 330/1996; FKFP 1043/1997; AMFK 707/96; PFP-4077/1997, by the Soros Foundation, and by Biogal-Teva. I.F. was supported by the Arlene and Marshall Bennett Research Fund of the Division of Neurosurgery, Evanston Northwestern Healthcare.

    • Abbreviations used are::
      F
      blood flow
      AIB
      α-aminoisobutyric acid
      DTS
      direct tissue sampling
      IAP
      iodoantipyrine
      IC
      intracerebral
      K
      transcapillary transfer constant
      LSC
      liquid scintillation counting
      PS
      permeability-surface area product
      P
      permeability constant
      ROI
      region of interest
      QAR
      quantitative autoradiography
      SL-QAR
      single label quantitative autoradiographic
      PLM
      percent labeled mitosis
      TAT
      tissue adjacent to tumor
      • Received November 6, 1998.
      • Accepted June 14, 1999.
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    1. DMD September 1, 1999 vol. 27 no. 9 1085-1091
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