Vascular Endothelial Growth Factor C–Induced Lymphangiogenesis DecreasesTumor Interstitial Fluid Pressure and Tumor Growth1
Identifieur interne : 003211 ( Pmc/Curation ); précédent : 003210; suivant : 003212Vascular Endothelial Growth Factor C–Induced Lymphangiogenesis DecreasesTumor Interstitial Fluid Pressure and Tumor Growth1
Auteurs : Matthias Hofmann [Allemagne] ; Ralph Pflanzer [Allemagne] ; Nadja Nicole Zoller [Allemagne] ; August Bernd [Allemagne] ; Roland Kaufmann [Allemagne] ; Diamant Thaci [Allemagne] ; Jurgen Bereiter-Hahn [Allemagne] ; Satoshi Hirohata [Japon] ; Stefan Kippenberger [Allemagne]Source :
- Translational Oncology [ 1936-5233 ] ; 2013.
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
Url:
PubMed: 23908682
PubMed Central: 3730014
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<front><div type="abstract" xml:lang="en"><p>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 <italic>in vivo</italic>
.</p>
</div>
</front>
</TEI>
<pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Transl Oncol</journal-id>
<journal-id journal-id-type="iso-abbrev">Transl Oncol</journal-id>
<journal-id journal-id-type="publisher-id">TLO</journal-id>
<journal-title-group><journal-title>Translational Oncology</journal-title>
</journal-title-group>
<issn pub-type="epub">1936-5233</issn>
<publisher><publisher-name>Neoplasia Press Inc.</publisher-name>
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<article-id pub-id-type="pmc">3730014</article-id>
<article-id pub-id-type="publisher-id">13274</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Brief Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Vascular Endothelial Growth Factor C–Induced Lymphangiogenesis DecreasesTumor Interstitial Fluid Pressure and Tumor Growth<xref ref-type="fn" rid="FN1">1</xref>
</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Hofmann</surname>
<given-names>Matthias</given-names>
</name>
<xref ref-type="aff" rid="A1">*</xref>
<xref ref-type="author-notes" rid="FN2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Pflanzer</surname>
<given-names>Ralph</given-names>
</name>
<xref ref-type="aff" rid="A1">*</xref>
<xref ref-type="author-notes" rid="FN2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Zoller</surname>
<given-names>Nadja Nicole</given-names>
</name>
<xref ref-type="aff" rid="A1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Bernd</surname>
<given-names>August</given-names>
</name>
<xref ref-type="aff" rid="A1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kaufmann</surname>
<given-names>Roland</given-names>
</name>
<xref ref-type="aff" rid="A1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Thaci</surname>
<given-names>Diamant</given-names>
</name>
<xref ref-type="aff" rid="A1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Bereiter-Hahn</surname>
<given-names>Jurgen</given-names>
</name>
<xref ref-type="aff" rid="A2">†</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hirohata</surname>
<given-names>Satoshi</given-names>
</name>
<xref ref-type="aff" rid="A3">‡</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kippenberger</surname>
<given-names>Stefan</given-names>
</name>
<xref ref-type="aff" rid="A1">*</xref>
</contrib>
</contrib-group>
<aff id="A1"><label>*</label>
Department of Dermatology, Venereology and Allergology, Goethe University, Frankfurt/Main, Germany</aff>
<aff id="A2"><label>†</label>
Kinematic Cell Research Group, Department of Cell Biology and Neurosciences, Goethe University, Frankfurt/Main, Germany</aff>
<aff id="A3"><label>‡</label>
Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan</aff>
<author-notes><corresp>Address all correspondence to: Matthias Hofmann, PhD, Department of Dermatology, Venereology and Allergology, Johann Wolfgang Goethe University, Theodor-Stern Kai 7, D-60590 Frankfurt/Main, Germany. E-mail: <email>Matthias.Hofmann@em.uni-frankfurt.de</email>
</corresp>
<fn fn-type="equal" id="FN2"><label>2</label>
<p>These authors contributed equally to this work.</p>
</fn>
</author-notes>
<pub-date pub-type="epub"><day>1</day>
<month>8</month>
<year>2013</year>
</pub-date>
<pub-date pub-type="collection"><month>8</month>
<year>2013</year>
</pub-date>
<volume>6</volume>
<issue>4</issue>
<fpage>398</fpage>
<lpage>404</lpage>
<history><date date-type="received"><day>11</day>
<month>3</month>
<year>2013</year>
</date>
<date date-type="rev-recd"><day>7</day>
<month>5</month>
<year>2013</year>
</date>
<date date-type="accepted"><day>14</day>
<month>5</month>
<year>2013</year>
</date>
</history>
<permissions><copyright-statement>Copyright © 2013 Neoplasia Press, Inc. All rights reserved</copyright-statement>
<copyright-year>2013</copyright-year>
</permissions>
<abstract><p>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 <italic>in vivo</italic>
.</p>
</abstract>
</article-meta>
</front>
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