---
_id: '54932'
abstract:
- lang: eng
  text: Incubation of microvascular endothelial cells with combretastatin A-4 phosphate
    (CA-4P), a microtubule-destabilizing compound that preferentially targets tumor
    vessels, altered cell morphology and induced scattering of Golgi stacks. Concomitantly,
    CA-4P up-regulated connective tissue growth factor (CTGF/CCN2), a pleiotropic
    factor with antiangiogenic properties. In contrast to the effects of other microtubule-targeting
    agents such as colchicine or nocodazole, up-regulation of CTGF was only detectable
    in sparse cells, which were not embedded in a cell monolayer. Furthermore, CA-4P
    induced CTGF expression in endothelial cells, forming tube-like structures on
    basement membrane gels. Up-regulation of CTGF by CA-4P was dependent on Rho kinase
    signaling and was increased when p42/44 mitogen-activated protein kinase was inhibited.
    Additionally, FoxO transcription factors were identified as potent regulators
    of CTGF expression in endothelial cells. Activation of FoxO transcription factors
    by inhibition of phosphatidylinositol 3-kinase/AKT signaling resulted in a synergistic
    increase in CA-4P-mediated CTGF induction. CA-4P-mediated expression of CTGF was
    thus potentiated by the inhibition of kinase pathways, which are targets of novel
    antineoplastic drugs. Up-regulation of CTGF by low concentrations of CA-4P may
    thus occur in newly formed tumor vessels and contribute to the microvessel destabilization
    and antiangiogenic effects of CA-4P observed in vivo.
author:
- first_name: Jana
  full_name: Samarin, Jana
  last_name: Samarin
- first_name: Margot
  full_name: Rehm, Margot
  last_name: Rehm
- first_name: Bettina
  full_name: Krueger, Bettina
  id: '49428'
  last_name: Krueger
  orcid: 0000-0001-5351-1785
- first_name: Jens
  full_name: Waschke, Jens
  last_name: Waschke
- first_name: Margarete
  full_name: Goppelt-Struebe, Margarete
  last_name: Goppelt-Struebe
citation:
  ama: Samarin J, Rehm M, Krueger B, Waschke J, Goppelt-Struebe M. Up-Regulation of
    Connective Tissue Growth Factor in Endothelial Cells by the Microtubule-Destabilizing
    Agent Combretastatin A-4. <i>Molecular Cancer Research</i>. 2009;7(2):180–188.
    doi:<a href="https://doi.org/10.1158/1541-7786.mcr-08-0292">10.1158/1541-7786.mcr-08-0292</a>
  apa: Samarin, J., Rehm, M., Krueger, B., Waschke, J., &#38; Goppelt-Struebe, M.
    (2009). Up-Regulation of Connective Tissue Growth Factor in Endothelial Cells
    by the Microtubule-Destabilizing Agent Combretastatin A-4. <i>Molecular Cancer
    Research</i>, <i>7</i>(2), 180–188. <a href="https://doi.org/10.1158/1541-7786.mcr-08-0292">https://doi.org/10.1158/1541-7786.mcr-08-0292</a>
  bibtex: '@article{Samarin_Rehm_Krueger_Waschke_Goppelt-Struebe_2009, title={Up-Regulation
    of Connective Tissue Growth Factor in Endothelial Cells by the Microtubule-Destabilizing
    Agent Combretastatin A-4}, volume={7}, DOI={<a href="https://doi.org/10.1158/1541-7786.mcr-08-0292">10.1158/1541-7786.mcr-08-0292</a>},
    number={2}, journal={Molecular Cancer Research}, publisher={American Association
    for Cancer Research (AACR)}, author={Samarin, Jana and Rehm, Margot and Krueger,
    Bettina and Waschke, Jens and Goppelt-Struebe, Margarete}, year={2009}, pages={180–188}
    }'
  chicago: 'Samarin, Jana, Margot Rehm, Bettina Krueger, Jens Waschke, and Margarete
    Goppelt-Struebe. “Up-Regulation of Connective Tissue Growth Factor in Endothelial
    Cells by the Microtubule-Destabilizing Agent Combretastatin A-4.” <i>Molecular
    Cancer Research</i> 7, no. 2 (2009): 180–188. <a href="https://doi.org/10.1158/1541-7786.mcr-08-0292">https://doi.org/10.1158/1541-7786.mcr-08-0292</a>.'
  ieee: 'J. Samarin, M. Rehm, B. Krueger, J. Waschke, and M. Goppelt-Struebe, “Up-Regulation
    of Connective Tissue Growth Factor in Endothelial Cells by the Microtubule-Destabilizing
    Agent Combretastatin A-4,” <i>Molecular Cancer Research</i>, vol. 7, no. 2, pp.
    180–188, 2009, doi: <a href="https://doi.org/10.1158/1541-7786.mcr-08-0292">10.1158/1541-7786.mcr-08-0292</a>.'
  mla: Samarin, Jana, et al. “Up-Regulation of Connective Tissue Growth Factor in
    Endothelial Cells by the Microtubule-Destabilizing Agent Combretastatin A-4.”
    <i>Molecular Cancer Research</i>, vol. 7, no. 2, American Association for Cancer
    Research (AACR), 2009, pp. 180–188, doi:<a href="https://doi.org/10.1158/1541-7786.mcr-08-0292">10.1158/1541-7786.mcr-08-0292</a>.
  short: J. Samarin, M. Rehm, B. Krueger, J. Waschke, M. Goppelt-Struebe, Molecular
    Cancer Research 7 (2009) 180–188.
date_created: 2024-06-30T13:47:10Z
date_updated: 2024-06-30T13:47:22Z
department:
- _id: '35'
- _id: '22'
doi: 10.1158/1541-7786.mcr-08-0292
intvolume: '         7'
issue: '2'
language:
- iso: eng
page: 180–188
publication: Molecular Cancer Research
publisher: American Association for Cancer Research (AACR)
status: public
title: Up-Regulation of Connective Tissue Growth Factor in Endothelial Cells by the
  Microtubule-Destabilizing Agent Combretastatin A-4
type: journal_article
user_id: '49428'
volume: 7
year: '2009'
...