Netrin-4 regulates angiogenic responses and tumor cell growth
- Genzyme Corporation, 49 New York Avenue, Framingham, MA 01701 (United States)
Netrin-4 is a 628 amino acid basement membrane component that promotes neurite elongation at low concentrations but inhibits neurite extension at high concentrations. There is a growing body of literature suggesting that several molecules, including netrins, are regulators of both neuronal and vascular growth. It is believed that molecules that guide neural growth and development are also involved in regulating morphogenesis of the vascular tree. Further, netrins have recently been implicated in controlling epithelial cell branching morphogenesis in the breast, lung and pancreas. Characterization of purified netrin-4 in in vitro angiogenesis assays demonstrated that netrin-4 markedly inhibits HMVEC migration and tube formation. Moreover, netrin-4 inhibits proliferation of a variety of human tumor cells in vitro. Netrin-4 has only modest effects on proliferation of endothelial and other non-transformed cells. Netrin-4 treatment results in phosphorylation changes of proteins that are known to control cell growth. Specifically, Phospho-Akt-1, Phospho-Jnk-2, and Phospho-c-Jun are reduced in tumor cells that have been treated with netrin-4. Together, these data suggest a potential role for netrin-4 in regulating tumor growth.
- OSTI ID:
- 21176181
- Journal Information:
- Experimental Cell Research, Vol. 315, Issue 5; Other Information: DOI: 10.1016/j.yexcr.2008.11.018; PII: S0014-4827(08)00508-9; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0014-4827
- Country of Publication:
- United States
- Language:
- English
Similar Records
Dissociation of ERK and Akt signaling in endothelial cell angiogenic responses to {beta}-amyloid
The inhibition of MAPK potentiates the anti-angiogenic efficacy of mTOR inhibitors