Trefoil peptides as proangiogenic factors in vivo and in vitro: Implication of cyclooxygenase-2 and EGF receptor signaling

Sylvie Rodrigues, Elisabeth Van Aken, Saskia Van Bocxlaer, Samir Attoub, Quang Dé Nguyen, Erik Bruyneel, Bruce R. Westley, Felicity E.B. May, Lars Thim, Marc Mareel, Christian Gespach, Shahin Emami

Research output: Contribution to journalArticlepeer-review

123 Citations (Scopus)

Abstract

We previously established that the trefoil peptides (TFFs) pS2, spasmolytic polypeptide, and intestinal trefoil factor are involved in cellular scattering and invasion in kidney and colonic cancer cells. Using the chorioallantoic membrane (CAM) assay and the formation of tube-like structures by human umbilical vein endothelial cells (HUVEC) plated on the Matrigel matrix substratum, we report here that TFFs are proangiogenic factors. Angiogenic activity of TFFs is comparable to that induced by vascular endothelial growth factor, leptin, and transforming growth factor-α. Stimulation of angiogenesis by pS2 in the CAM assay is blocked by pharmacological inhibitors of cyclooxygenase COX-2 (NS-398) and epidermal growth factor receptor (EGF-R) tyrosine kinase (ZD1839), but is independent of KDR/Flk-1 and thromboxane A2 receptors. In contrast, the morphogenic switch induced by pS2 in HUVEC cells could be inhibited by the specific KDR heptapeptide antagonist ATWLPPR and by inhibitors of COX-2 and EGF-R signaling. These results implicate TFFs in the formation of new blood vessels during normal and pathophysiological processes linked to wound healing, inflammation, and cancer progression in the digestive mucosa and other human solid tumors associated with aberrant expression of TFFs. - Rodrigues, S., Van Aken, E., Van Bocxlaer, S., Attoub, S., Nguyen, Q.-D., Bruyneel, E., Westley, B. R., May, F. E. B., Thim, L., Mareel, M., Gespach, C., Emami, S. Trefoil peptides as proangiogenic factors in vivo and in vitro: implication of cylooxygenase-2 and EGF receptor signaling.

Original languageEnglish
Pages (from-to)7-16
Number of pages10
JournalFASEB Journal
Volume17
Issue number1
DOIs
Publication statusPublished - Jan 1 2003
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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