Review Signalling pathways in vasculogenic mimicry Yvette W.J. Paulis a,b , Patricia M.M.B. Soetekouw a , Henk M.W. Verheul b , Vivianne C.G. Tjan-Heijnen a , Arjan W. Griffioen b, ⁎ a Department of Internal Medicine, Division of Medical Oncology, School for Oncology and Developmental Biology (GROW), Maastricht University Medical Center, Maastricht, The Netherlands b Angiogenesis Laboratory, Department of Medical Oncology, VU University Medical Center, De Boelelaan 1117, Amsterdam, The Netherlands abstract article info Article history: Received 30 October 2009 Received in revised form 24 December 2009 Accepted 7 January 2010 Available online xxxx Keywords: Angiogenesis Cancer Plasticity Signalling pathways Vasculogenesis Vasculogenic mimicry Solid tumour growth is dependent on the development of an adequate blood supply. For years, sprouting angiogenesis has been considered an exclusive mechanism of tumour vascularization. However, over the last years, several other mechanisms have been identified, including vessel-co-option, intussusception, recruitment of endothelial precursor cells (EPCs) and even mechanisms that do not involve endothelial cells, a process called vasculogenic mimicry (VM). The latter describes a mechanism by which highly aggressive tumour cells can form vessel-like structures themselves, by virtue of their high plasticity. VM has been observed in several tumour types and its occurrence is strongly associated with a poor prognosis. This review will focus on signalling molecules and cascades involved in VM. In addition, we will discuss the presence of VM in relation to ongoing cancer research. Finally, we describe the clinical significance of VM regarding anti-angiogenesis treatment modalities. © 2010 Elsevier B.V. All rights reserved. Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 2. Functional relevance of vasculogenic mimicry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 3. Signalling cascades involved in vasculogenic mimicry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 3.1. Key VM signalling pathways . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 3.2. Cyclic AMP signalling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 3.3. Tumour galectins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 3.4. Signalling molecules in embryonic vasculogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 3.4.1. Nodal/Notch . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 3.4.2. Wingless . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 4. Biological phenomenon related to vasculogenic mimicry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 4.1. Cancer stem cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 4.2. Endothelial cell mutation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 5. Clinical significance of vasculogenic mimicry. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 6. Concluding remarks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 1. Introduction Vasculogenic mimicry (VM) was introduced in 1999 and described the unique ability of highly aggressive melanoma cells to dedifferentiate into multiple cellular phenotypes, and obtain endothelial-like characteristics [1]. This process would then lead to the formation of de novo vasculogenic-like matrix-embedded networks, i.e. vascular-like struc- tures, containing plasma and red blood cells [1,2], and ultimately con- tributing to blood circulation. Morphological characterization revealed that VM networks are rich in laminin and lined by tumour cells [1–3], thereby encircling spheroidal nests of tumour cells. Within the matrix- rich channels endothelial cells were not identified by light microscopy, transmission electron microscopy, or by immunohistochemistry [1]. Biochimica et Biophysica Acta xxx (2010) xxx–xxx ⁎ Corresponding author. VU University Medical Center, Department of Medical Oncology – Angiogenesis Laboratory, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands. Tel.: +31 20 4443374; fax: +31 20 4443844. E-mail address: aw.griffioen@vumc.nl (A.W. Griffioen). BBACAN-87740; No. of pages: 11; 4C: 4 0304-419X/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.bbcan.2010.01.001 Contents lists available at ScienceDirect Biochimica et Biophysica Acta journal homepage: www.elsevier.com/locate/bbacan ARTICLE IN PRESS Please cite this article as: Y.W.J. Paulis, et al., Signalling pathways in vasculogenic mimicry, Biochim. Biophys. Acta (2010), doi:10.1016/j. bbcan.2010.01.001