Interstitial permeability and elasticity in human cervix cancer

Abstract

Malignant tumors are characterized by abnormalities of the vasculature and interstitium, which may impede the distribution of drugs and imaging agents. Here we describe a method for estimating tumor interstitial permeability and elasticity based on fitting a spatio-temporal fluid dynamic model to the time course of interstitial pressure (IFP) measurements. The model assumes that sudden insertion of the IFP measurement needle transiently perturbs the steady-state fluid balance, which recovers over time as a function of the vascular and interstitial hydraulic conductivities ( L p S and K), the interstitial bulk modulus ( E) and the extracellular, extravascular volume fraction ( φ). Initial simulations showed that the time course of IFP recordings was mainly determined by K and E/ φ. Mean values of K and E/ φ in 60 newly diagnosed cervix cancers were 1.5 × 10 − 7 (SE 2.2 × 10 − 8 ) cm 2/mm Hg s and 2230 (SE 212) mm Hg, respectively. For comparison, K and E/ φ were also measured in orthotopic ME-180 human cervix cancer xenografts and KHT-C fibrosarcomas in mice. K was higher in both of these tumors (7.0 × 10 − 7 and 9.3 × 10 − 7 ) than in cervix cancer, and E/ φ was lower (497 and 433). To our knowledge, these are the first measurements of interstitial permeability and elasticity in individual human cancers. Serial evaluation of these parameters may provide a means of clinically monitoring response to treatments that specifically target the tumor microenvironment.