Interstitial Fluid Pressure and Vascularity of Intradermal and Intramuscular Human Tumor Xenografts

Abstract

High interstitial fluid pressure (IFP) in tumors has been shown to be associated with poor prognosis. Mechanisms underlying the intertumor heterogeneity in IFP were investigated in this study. A-07 melanoma xenografts were transplanted intradermally or intramuscularly in BALB/c nu/nu mice. IFP was measured in the center of the tumors with a Millar catheter. Tumor blood perfusion and extracellular volume fraction were assessed by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). The necrotic fraction, vascular density, and vessel diameters of the tumors were determined by image analysis of histological preparations. Significant intertumor heterogeneity in IFP, blood perfusion, and microvascular morphology was observed whether the tumors were transplanted intradermally or intramuscularly. High IFP was mainly a consequence of high resistance to blood flow caused by low vessel diameters in either transplantation site. IFP decreased with increasing blood perfusion in intradermal tumors and increased with increasing blood perfusion in intramuscular tumors, mainly because the morphology of the tumor microvasculature differed systematically between the two tumor models. The potential of DCE-MRI as a noninvasive method for assessing the IFP of tumors may be limited because any relationship between IFP and blood perfusion may differ with the tumor growth site.