Angiogenic vascular growth in the rat peritoneal disseminated tumor model

The objective of this study was to provide the first quantitative measurements of the process of vascular growth in the rat peritoneal disseminated tumor model in both arteriolar and venular systems. Male Fischer 344 rats were injected intraperitoneally with 1 x 10(7) cells of colon carcinoma cell line (RCN-9). Three to eleven days after tumor cell inoculation, the rats were subjected to intravital microscopic observation of the mesenteric microcirculation. Accompanying tumor growth, mesenteric windows showed a marked neovascularization. The branching pattern of the vascular network was analyzed based on Horton's law of bifurcation. Arterioles and venules were given an order of branching separately according to the Strahler's nomenclature, and the number of vessel segments (N) having the same order number was counted. A vascular density index (VDI) and a bifurcation ratio (BR) were calculated from a semilogarithmic plot of the vessel density (dividing N by the vascularized area) against vessel order. Values of the VDI in venules (3.1 +/- 0.3 in the tumor-free rats, mean +/- SEM, n = 6) were found to be larger than those in arterioles (1.8 +/- 0.2). These values in both arterioles and venules showed a significant increase with time after the tumor cell inoculation (in venules, 12.3 +/- 1.1 at 9-11 days after the tumor cell inoculation; in arterioles, 5.7 +/- 0.7). Moreover, the rate of increase in the venular VDI was larger than that of the arteriolar VDI. The arteriolar BR remained almost constant (3.8 +/- 0.2 for the tumor-free rats and 4.1 +/- 0.1 for 9-11 days after tumor cell inoculation), whereas the venular BR showed an increase with time (3.0 +/- 0.1 and 3.8 +/- 0.2, respectively). In conclusion, a marked angiogenesis was observed in the mesentery of the rats bearing peritoneal tumors. Neovascularization was found to occur predominantly in the venular system.