Vascular endothelial growth factor C-induced lymphangiogenesis decreases tumor interstitial fluid pressure and tumor

Matthias Hofmann, Ralph Pflanzer, Nadja Nicole Zöller, August Bernd, Roland Kaufmann, Diamant Thaci, Jürgen Bereiter-Hahn, Satoshi Hirohata, Stefan Kippenberger

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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.

Original languageEnglish
Pages (from-to)398-404
Number of pages7
JournalTranslational Oncology
Volume6
Issue number4
DOIs
Publication statusPublished - Aug 2013

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Hofmann, M., Pflanzer, R., Zöller, N. N., Bernd, A., Kaufmann, R., Thaci, D., Bereiter-Hahn, J., Hirohata, S., & Kippenberger, S. (2013). Vascular endothelial growth factor C-induced lymphangiogenesis decreases tumor interstitial fluid pressure and tumor. Translational Oncology, 6(4), 398-404. https://doi.org/10.1593/tlo.13274