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Angiomotin expression promotes hemangioendothelioma invasion

Oncogene volume 23, pages 1469–1473 (2004)Cite this article

Abstract

Angiomotin was identified by its ability to bind angiostatin and has been shown to mediate its activity in vitro. The family of angiomotin-like protein consists of three members that have coiled-coil domains and conserved c-terminal PDZ-binding motifs. We show here that expression of angiomotin in mouse aortic endothelial (MAE) cells results in stabilization of tubes in the Matrigel assay. Control tubes start to regress after 72 h, whereas MAE-angiomotin (MAE Amot) tubes were stable for over 30 days. In contrast, cells expressing a functional mutant lacking the PDZ protein interaction motif did not migrate and form tubes. Cells from the established tubes invaded into the solidified matrigel. We therefore tested whether angiomotin promotes endothelial invasion. In microcarrier-based invasion in vitro assay, angiomotin-expressing cells invaded collagen matrix and formed tube-like branches. This was confirmed in vivo as injection of MAE-Amot cells promoted tumor growth and invasion into surrounding muscle tissue. Injection of cells transfected with the functional mutant resulted in establishment of noninvasive tumors surrounded by a capsule of fibrous tissue. These tumors remained in constant size or dormant over 3 weeks. Zymogel analysis of the transfected cells did not reveal any differences in proteolytic activity. However, time-lapse photography showed a significant increase in random motility in MAE-Amot cells. We conclude that angiomotin may promote angiogenesis by both stimulating invasion as well as stabilizing established tubes.

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Acknowledgements

This work was supported by American Skin Association, the Atorvastastin Research Award (Pfizer) and NIAMS, National Institutes of Health, Grant AR44947 (to J.L.A.), Emory Skin Disease Research Core Center P30, and National Institutes of Health Grants AR42687 and AR02030 (to J.L.A).

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Authors and Affiliations

  1. Department of Oncology-Pathology, Cancer Centre Karolinska Institute, Stockholm, S-17176, Sweden

    Tetyana Levchenko, Anders Bratt & Lars Holmgren

  2. Department of Dermatology, Emory University School of Medicine, Atlanta, 30322, Georgia, USA

    Jack L Arbiser

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  1. Tetyana Levchenko
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  2. Anders Bratt
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  3. Jack L Arbiser
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  4. Lars Holmgren
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Correspondence to Lars Holmgren.

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Levchenko, T., Bratt, A., Arbiser, J. et al. Angiomotin expression promotes hemangioendothelioma invasion. Oncogene 23, 1469–1473 (2004). https://doi.org/10.1038/sj.onc.1207264

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