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Cellular and Molecular Biology of Cancer Cell Extravasation

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Signaling Pathways and Molecular Mediators in Metastasis

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Abstract

Hematogenous metastasis involves the entry of cancer cells into the circulation at a primary tumor site and the extravasation of those cells at a secondary organ which may ultimately support the growth of a metastatic tumor. Although extravasation is likely an obligate step in metastasis, it is relatively poorly understood in part due the difficulty studying this process in appropriate experimental models in vivo. Thus, there remain open questions about how cancer cells interact with the vascular wall during this process including the extent to which non-selective mechanisms such as size restriction versus specific adhesive interactions determine the behavior of extravasating cancer cells; how cancer cells cross the endothelium; and the degree to which extravasation limits the overall efficiency of metastasis. The answers to these questions are influenced by specific properties of both the cancer cells and the nature of the vascular bed involved. In this Chapter, we review our current understanding of the cellular and molecular biology of cancer cell extravasation and discuss how this knowledge impacts clinical issues related to the biology of circulating tumor cells and cancer therapy.

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Abbreviations

CTC:

Circulating tumor cell

DTC:

Disseminated tumor cell

EMT:

Epithelial-to-mesenchymal transition

EpCAM:

Epithelial cell adhesion molecule

MET:

Mesenchymal-to-epithelial transition

SCID:

Severe and combined immune deficient

TEM:

Trans-endothelial migration

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Acknowledgements

We thank Jones Nauseef for critical reading of the manuscript. JMB was supported by a Department of Defense pre-doctoral fellowship, PC094754. Work on cancer cell extravasation in the Henry lab has been supported by a Grant-in-Aid from the American Heart Association.

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Authors and Affiliations

  1. Departments of Molecular Physiology and Biophysics and Pathology, Holden Comprehensive Cancer Center, University of Iowa Carver College of Medicine, Iowa City, IA, USA

    J. Matthew Barnes & Michael D. Henry

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  1. J. Matthew Barnes
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  2. Michael D. Henry
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Correspondence to Michael D. Henry .

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  1. Drexel University College of Medicine, N. 15th Street 245, Philadelphia, 19102, Pennsylvania, USA

    Alessandro Fatatis

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Barnes, J.M., Henry, M.D. (2011). Cellular and Molecular Biology of Cancer Cell Extravasation. In: Fatatis, A. (eds) Signaling Pathways and Molecular Mediators in Metastasis. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2558-4_8

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