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17β-Estradiol-Mediated Vessel Assembly and Stabilization in Tumor Angiogenesis Requires TGFβ and EGFR Crosstalk

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Abstract

It is widely established that angiogenesis is required during tumor progression. Emerging data, suggests that estrogens can mediate endothelial proliferation and differentiation. We investigated the role of estrogens in the formation and stabilization of capillary-like structures, and identified 17β-estradiol-driven pathways involved in vessel assembly. We show that estrogens induce MCF7 breast cancer cells to secrete TGFβ1. In addition, TGFβ cross talks with EGFR signaling pathway with concomitant up-regulation of EGFR ligand, TGFα, promoting cord-like formations in HUVEC cultures. The action of 17β-estradiol was not restricted to endothelium, since 17β-estradiol also stimulated recovery and migration of a smooth muscle cell line (FLTR) to injured areas again by the cross talk between these two signaling pathways. Finally, given the relevant role of 17β-estradiol in vessel stabilization, co-cultures of HUVEC and FLTR cells were established in the presence of 17β-estradiol or TGFβ1. By blocking TGFβ or EGFR signaling, we demonstrate that 17β-estradiol promoted vessel stabilization through the interplay of TGFβ1 and EGFR signaling transduction pathways. Our data suggest that estrogen mediates endothelial cell stabilization and vessel assembly. These vessel protective effects involve TGFβ1 and EGFR signaling transduction pathways.

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Authors and Affiliations

  1. Portuguese Institute of Oncology, R. Antonio B. Almeida, Porto, Portugal

    Raquel Soares

  2. Medical Faculty, University of Porto, Al. Prof Hernani Monteiro, Porto, Portugal

    Raquel Soares & Fernando C. Schmitt

  3. IPATIMUP, Institute of Molecular Pathology and Immunology of the University of Porto, R. Roberto Frias s/n, 4200, Porto, Portugal

    Raquel Soares

  4. Breast Cancer Research Lab., Fox Chase Cancer Center, Philadelphia, USA

    Shanchun Guo & Jose Russo

  5. IPATIMUP, Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal

    Fátima Gärtner & Fernando C. Schmitt

  6. ICBAS – Instituto de Ciências Biomédicas Abel Salazar, Porto, Portugal

    Fátima Gärtner

Authors
  1. Raquel Soares
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  2. Shanchun Guo
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  3. Fátima Gärtner
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  4. Fernando C. Schmitt
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  5. Jose Russo
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Correspondence to Raquel Soares.

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Soares, R., Guo, S., Gärtner, F. et al. 17β-Estradiol-Mediated Vessel Assembly and Stabilization in Tumor Angiogenesis Requires TGFβ and EGFR Crosstalk. Angiogenesis 6, 271–281 (2003). https://doi.org/10.1023/B:AGEN.0000029413.32882.dd

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  • DOI: https://doi.org/10.1023/B:AGEN.0000029413.32882.dd

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