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More Than a Barrier: How the Endothelium Instructs Metastasis

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Biomarkers of the Tumor Microenvironment

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Abstract

For metastasis to occur, a tumor cell must interact with endothelium at many steps and on multiple levels. The first half of this chapter highlights specific ligand–receptor interactions between tumor cells and the endothelium required for successful metastatic dissemination to occur, with an eye on how the specificity of endothelium influences this process in different tissues. The second half of this chapter focuses on interactions between disseminated tumor cells (DTCs) and endothelium post-extravasation. Evidence that a niche comprised by microvasculature is responsible for both maintaining cellular dormancy and facilitating tumor cell outgrowth is presented. By contrasting these studies with the known roles of endothelial-derived signals in development, maintenance of organ homeostasis, wound healing, and in stem cell niches, we describe how endothelium could dictate these opposing cellular responses during metastasis. Elaborating upon the role of endothelium as a regulator of DTC dormancy and outgrowth in multiple tissues—perhaps for multiple cancers—will guide development of therapies to combat and even prevent metastasis.

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Abbreviations

ADAM:

A disintegrin and metalloproteinase

Aes:

Amino-terminal enhancer of split

ATP:

Adenosine triphosphate

BBB:

Blood–brain barrier

CXCL12:

Chemokine (C-X-C Motif) ligand 12

CXCR7:

C-X-C chemokine receptor type 7

Dll4:

Delta-like protein 4

DTC:

Disseminated tumor cell

EC:

Endothelial cell

ECM:

Extracellular matrix

EGF:

Epidermal growth factor

Eph:

Ephrin

HB-EGF:

Heparin-binding EGF-like growth factor

HSC:

Hematopoietic stem cell

HSPC:

Hematopoietic stem and progenitor cell

ICAM-1:

Intercellular adhesion molecule 1

IgG:

Immunoglobulin

IL:

Interleukin

L1CAM:

L1 cell adhesion molecule

LGALS3BP:

Galectin-3-binding protein

LSEC:

Liver sinusoidal endothelial cell

MAPK:

Mitogen-activated protein kinase

MENAINV :

Mammalian enabled homologue, invasion

MLCK:

Myosin light chain kinase

NO:

Nitric oxide

NSC:

Neural stem cell

PDGF:

Platelet-derived growth factor

PECAM:

Platelet endothelial cell adhesion molecule

POSTN:

Periostin

PSGL1:

P-selectin glycoprotein ligand 1

PVN:

Perivascular niche

SCF:

Stem cell factor

sLex :

Tetrasaccharide sialyl Lewis x antigen

SVZ:

Subventricular zone

TGF:

Transforming growth factor

TMEM:

Tumor microenvironment of metastasis

TNFα:

Tumor necrosis factor-α

TSP-1:

Thrombospondin-1

VCAM-1:

Vascular cell adhesion molecule 1

VEGF:

Vascular endothelial growth factor

VEGFR:

Vascular endothelial growth factor receptor

vWF:

Von Willebrand factor

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  1. Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, M5-A864, Seattle, WA, 98109, USA

    Candice Alexandra Grzelak, Andrea Rachel Lim & Cyrus Michael Ghajar

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  1. Candice Alexandra Grzelak
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  2. Andrea Rachel Lim
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Correspondence to Cyrus Michael Ghajar .

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  1. Centre for Cancer Biomarkers CCBIO, Department of Clinical Medicine, University of Bergen, Bergen, Norway

    Lars A. Akslen

  2. Vascular Biology Program, Department of Surgery, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA

    Randolph S. Watnick

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Grzelak, C.A., Lim, A.R., Ghajar, C.M. (2017). More Than a Barrier: How the Endothelium Instructs Metastasis. In: Akslen, L., Watnick, R. (eds) Biomarkers of the Tumor Microenvironment. Springer, Cham. https://doi.org/10.1007/978-3-319-39147-2_2

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