article Jana Samarin author Margot Rehm author Bettina Krueger author 494280000-0001-5351-1785 Jens Waschke author Margarete Goppelt-Struebe author 35 department 22 department 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. American Association for Cancer Research (AACR)2009 eng 10.1158/1541-7786.mcr-08-0292 72180–188 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>. 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> 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>. J. Samarin, M. Rehm, B. Krueger, J. Waschke, M. Goppelt-Struebe, Molecular Cancer Research 7 (2009) 180–188. 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>. @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} } 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> 549322024-06-30T13:47:10Z2024-06-30T13:47:22Z