Netrin-1 specifically enhances cell spreading on fibronectin in human glioblastoma cells.

Abstract

Netrins are secreted molecules and involved in axon guidance, cell migration and tumor development. Recent studies revealed that netrins perform novel functions in such processes as epithelial development and angiogenesis without operating through the classical netrin receptors, DCC (Deleted in Colorectal Cancer) and Unc5h. In the present study, we investigated the roles of netrin-1 and its receptors in cell spreading of human glioblastoma cells, and found that netrin-1 haptotactically enhanced fibronectin-induced cell spreading and focal adhesion formation in U373 glioblastoma cells. Netrin-1 binding to the U373 cell membrane was blocked by an antibody against alphav integrin subunit, but not by an anti-DCC or anti-Unc5h antibody. In addition, enhancement of the fibronectin response by netrin-1 was abrogated by a function blocking antibody against integrin alphavbeta3. Since the alphav subunit of the integrin family plays an important role in the pathophysiological aspects of cell migration, including tumor angiogenesis and metastasis, our data provide important insight into the molecular mechanism of netrin function.

• Authors: Hyun Kyoung Lee, In Ae Seo, Yoon Kyung Shin, Sang Hwa Lee, Su-Young Seo, Duk Joon Suh, Hwan Tae Park
• Journal: The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology (Korean J Physiol Pharmacol) Vol. 12 Issue 5 Pg. 225-30 (Oct 2008) ISSN: 2093-3827 [Electronic] Korea (South)
• PMID: 19967060 (Publication Type: Journal Article)