Lowering of tumoral interstitial fluid pressure by prostaglandin E1 is paralleled by an increased uptake of 51Cr-EDTA

Abstract

High intra-tumoral fluid pressure (TP(IF)) may impair uptake of anticancer drugs into tumors, contributing to poor efficiency in treatment of carcinomas. Here, we demonstrate that lowering of TP(IF) parallels increased transport of 51Cr-EDTA (m.w. 341) into tumor interstitium. Introduction of 15 μg prostaglandin E1 (PGE1) -methyl ester into the s.c. tissue surrounding transplanted rat colonic (PROb) carcinomas or chemically-induced rat mammary carcinomas, lowered TP(IF) by 30%. Transcapillary transport into the interstitium of PROb tumors quantified by microdialysis increased by 39.6% after PGE1 treatment 40 min prior to administration of 51Cr EDTA (n=6; p<0.05) compared to vehicle (n= 10). In mammary tumors, PGE1 increased transport into the tumors by 86.9% over controls (n= 16; p<0.05). Both tumors had well developed stroma containing collagen and hyaluronan. Our data demonstrate that adjuvant treatment with PGE1 lowers TP(IF), and enhances transport into the tumors. This principle may be of value as adjuvant therapy in treatment of solid malignancies with currently used anticancer drugs. (C) 2000 Wiley-Liss, Inc.