TUMOR ANGIOGENESIS AND INTERSTITIAL HYPERTENSION

Due to the high permeability of tumor vessels to fluids and plasma pro teins, the microvascular pressure (MVP) is the principal driving force for interstitial hypertension in solid tumors; as a result, hydrostat ic pressures between the microvascular and interstitial space are clos e to equilibrium, Based on these observations, we hypothesized that th e tumor interstitial fluid pressure (IFP) should increase following th e onset of angiogenesis. To this end, the relationship between IFP and tumor neovascularization was determined in the human colon adenocarci noma (LS174T) and the murine carcinoma (MCaIV) implanted in a transpar ent dorsal skin fold chamber in severe combined immunodeficient mice, Three stages in the development of the tumor neovasculature were chara cterized by intravital microscopy, Stage I tumors were avascular, stag e II was characterized by vascular sprouts and loops, and in stage III , the tumor vasculature was completely developed and blood Bow was obv ious, The IFP vias measured with micropipettes and a servo-null system , For both tumor types, the IFP in stage I tumors was close to 0 mm Hg , and IFP increased significantly from one stage to the nest. To furth er confirm that interstitial hypertension was associated with the deve lopment of the tumor vasculature, IFP was measured in LS174T spheroids . The mean pressure in spheroids was 0.2 +/- 0.3 mm Hg. In stage III t umors, the IFP was compared to the MVP. In MCAIV, the MVP was comparab le to the IFP; however, in LS174T the MVP was significantly higher tha n the IFP. In conclusion, the results demonstrate that avascular tumor s have atmospheric pressures and that tumor interstitial hypertension is associated with the development of the neovasculature.