Vol. 27, Issue 9, 1085-1091, September 1999

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

Peter Molnar,^{1 2} Istvan Fekete,^{1 3} Kurt E. Schlageter,^{1 4} Gregory D. Lapin,^{1 5 6} and Dennis R. Groothuis^{1 6 7}

Department of Neurology, Northwestern University Medical School, Evanston Northwestern Healthcare, Evanston, Illinois

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 -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) and K (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 and K 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 Results as 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.