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Angiotropism, pericytic mimicry and extravascular migratory metastasis: an embryogenesis-derived program of tumor spread

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Abstract

Intravascular dissemination of tumor cells is the accepted mechanism of cancer metastasis. However, the phenomenon of angiotropism, pericyte mimicry (PM), and extravascular migratory metastasis (EVMM) has questioned the concept that tumor cells metastasize exclusively via circulation within vascular channels. This new paradigm of cancer spread and metastasis suggests that metastatic cells employ embryonic mechanisms for attachment to the abluminal surfaces of blood vessels (angiotropism) and spread via continuous migration, competing with and replacing pericytes, i.e., pericyte mimicry (PM). This is an entirely extravascular phenomenon (i.e., extravascular migratory metastasis or EVMM) without entry (intravasation) into vascular channels. PM and EVMM have mainly been studied in melanoma but also occur in other cancer types. PM and EVMM appear to be a reversion to an embryogenesis-derived program. There are many analogies between embryogenesis and cancer progression, including the important role of laminins, epithelial–mesenchymal transition, and the re-activation of embryonic signals by cancer cells. Furthermore, there is no circulation of blood during the first trimester of embryogenesis, despite the fact that there is extensive migration of cells to distant sites and formation of organs and tissues during this period. Embryonic migration therefore is a continuous extravascular migration as are PM and EVMM, supporting the concept that these embryonic migratory events appear to recur abnormally during the metastatic process. Finally, the perivascular location of tumor cells intrinsically links PM to vascular co-option. Taken together, these two new paradigms may greatly influence the development of new effective therapeutics for metastasis. In particular, targeting embryonic factors linked to migration that are detected during cancer metastasis may be particularly relevant to PM/EVMM.

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Acknowledgements

We sincerely thank Maud Haon who designed the diagram for Fig. 1.

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Authors and Affiliations

  1. Department of Translational Research, Institut Curie, Paris, France

    Claire Lugassy & Raymond L. Barnhill

  2. Department of Molecular Medicine and Biochemistry, The George Washington School of Medicine, Washington, DC, USA

    Hynda K. Kleinman

  3. Translational Cancer Research Unit, GZA Hospitals, Sint-Augustinus, Antwerp, Belgium

    Peter B. Vermeulen

  4. Center for Oncological Research (CORE, Faculty of Medicine and Health Sciences), University of Antwerp, Wilrijk, Antwerp, Belgium

    Peter B. Vermeulen

  5. University of Paris, Réné Descartes Faculty of Medicine, Paris, France

    Raymond L. Barnhill

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  1. Claire Lugassy
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Correspondence to Claire Lugassy.

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Lugassy, C., Kleinman, H.K., Vermeulen, P.B. et al. Angiotropism, pericytic mimicry and extravascular migratory metastasis: an embryogenesis-derived program of tumor spread. Angiogenesis 23, 27–41 (2020). https://doi.org/10.1007/s10456-019-09695-9

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