17ß-Estradiol-mediated vessel assembly and stabilization in tumor angiogenesis requires TGFß and EGFR crosstalk

• Type: Article in International Scientific Journal
• Date: 2003

Authors

soares, r (Author) FMDUP; guo, s (Author) Other; gÿrtner, f (Author) Other; schmitt, fc (Author) FMUP; russo, j (Author) Other

Journal

Title: Angiogenesis

Vol. 6

Pages: 271-281

ISSN: 0969-6970

Publisher: Springer Nature

Indexing

ISI Web of Knowledge

Scopus - 44 Citations

Other information

Authenticus ID: P-007-F4C

DOI: 10.1023/b:agen.0000029413.32882.dd

Abstract (EN): 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 17ß-estradiol-driven pathways involved in vessel assembly. We show that estrogens induce MCF7 breast cancer cells to secrete TGFß1. In addition, TGFß cross talks with EGFR signaling pathway with concomitant up-regulation of EGFR ligand, TGF¿, promoting cord-like formations in HUVEC cultures. The action of 17ß-estradiol was not restricted to endothelium, since 17ß-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 17ß-estradiol in vessel stabilization, co-cultures of HUVEC and FLTR cells were established in the presence of 17ß-estradiol or TGFß1. By blocking TGFß or EGFR signaling, we demonstrate that 17ß-estradiol promoted vessel stabilization through the interplay of TGFß1 and EGFR signaling transduction pathways. Our data suggest that estrogen mediates endothelial cell stabilization and vessel assembly. These vessel protective effects involve TGFß1 and EGFR signaling transduction pathways.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11