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Updated: May 9, 2026
Three-dimensional Cell Culture Model for Measuring the Effects of Interstitial Fluid Flow on Tumor Cell Invasion
Published on: July 25, 2012
Vascular endothelial growth factor C-induced lymphangiogenesis decreases tumor interstitial fluid pressure and tumor
Matthias Hofmann1, Ralph Pflanzer, Nadja Nicole Zoller
1Department of Dermatology, Venereology and Allergology, Goethe University, Frankfurt/Main, Germany.
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.
Insights
Elevated tumor interstitial fluid pressure (TIFP) hinders drug delivery. Inducing lymphangiogenesis with vascular endothelial growth factor C (VEGF-C) effectively reduced TIFP and tumor growth in a mouse model.
Area of Science:
- Oncology
- Biomedical Engineering
- Vascular Biology
Background:
- Solid tumors often display elevated tumor interstitial fluid pressure (TIFP), impeding macromolecular therapeutic uptake.
- Tumor-associated lymphatic vessel abnormalities are key factors in developing and sustaining high TIFP.
- Reduced lymphatic drainage contributes to increased TIFP, negatively impacting drug delivery and tumor treatment.
Purpose of the Study:
- To investigate if enhancing tumor-associated lymphangiogenesis using vascular endothelial growth factor C (VEGF-C) can reduce TIFP.
- To explore VEGF-C as a novel mechanism for actively lowering TIFP through increased lymphatic drainage.
- To assess the impact of induced lymphangiogenesis on tumor growth and biomechanical properties.
Main Methods:
- A xenograft mouse model was established using human A431 epidermoid vulva carcinoma cells in NMRI nu/nu mice.
- Vascular endothelial growth factor C (VEGF-C) was administered peritumorally to induce lymphangiogenesis.
- Tumor growth and TIFP were monitored over time in VEGF-C-treated, VEGF-A-treated, and control groups.
Main Results:
- VEGF-C treatment significantly lowered TIFP compared to control and VEGF-A groups.
- Tumor growth was significantly reduced in VEGF-C-treated animals over time.
- Actively induced lymphangiogenesis demonstrated a capacity to lower TIFP in vivo.
Conclusions:
- This study demonstrates for the first time that induced lymphangiogenesis can effectively lower TIFP in a xenograft tumor model.
- VEGF-C-mediated lymphangiogenesis presents a novel strategy to modulate tumor biomechanical properties and enhance therapeutic delivery.
- The developed model offers a new approach for reducing TIFP and potentially improving treatment outcomes in solid tumors.
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