title: Vascular endothelial growth factor C-induced lymphangiogenesis decreases tumor interstitial fluid pressure and tumor.
abstract: Characteristically, most solid tumors exhibit an increased tumor interstitial fluid pressure (TIFP) that directly contributes to the lowered uptake of macromolecular therapeutics into the tumor interstitium. Abnormalities in the tumor-associated lymph vessels are a central brick in the development and prolonged sustaining of an increased TIFP. In the current study, vascular endothelial growth factor C (VEGF-C) was used to enhance tumor-associated lymphangiogenesis as a new mechanism to actively reduce the TIFP by increased lymphatic drainage of the tumor tissue. Human A431 epidermoid vulva carcinoma cells were inoculated in NMRI nu/nu mice to generate a xenograft mouse model. Seven days after tumor cell injection, VEGF-C was peritumorally injected to induce lymphangiogenesis. Tumor growth and TIFP was lowered significantly over time in VEGF-C-treated tumors in comparison to control or VEGF-A-treated animals. These data demonstrate for the first time that actively induced lymphangiogenesis can lower the TIFP in a xenograft tumor model and apparently reduce tumor growth. This model represents a novel approach to modulate biomechanical properties of the tumor interstitium enabling a lowering of TIFP in vivo.
authors.affiliation: Department of Dermatology, Venereology and Allergology, Goethe University, Frankfurt/Main, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Hofmann
authors.forename: Ralph
authors.initials: R
authors.lastname: Pflanzer
authors.forename: Nadja Nicole
authors.initials: NN
authors.lastname: Zoller
authors.forename: August
authors.initials: A
authors.lastname: Bernd
authors.forename: Roland
authors.initials: R
authors.lastname: Kaufmann
authors.forename: Diamant
authors.initials: D
authors.lastname: Thaci
authors.forename: Jurgen
authors.initials: J
authors.lastname: Bereiter-Hahn
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hirohata
authors.forename: Stefan
authors.initials: S
authors.lastname: Kippenberger
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