Open Access

ARTICLE

Tumor Cell Extravasation Mediated by Leukocyte Adhesion is Shear Rate Dependent on IL-8 Signaling^*

Shile Liang^†, Meghan Hoskins^†, Cheng Dong^‡

* An invited manuscript by the Editor-in-Chief, MCB, for a special issue in a celebration of Dr. Y.C. Fung’s 90^th birthday
† Department of Bioengineering, The Pennsylvania State University, University Park, PA 16802
‡ Corresponding author. Department of Bioengineering – 233 Hallowell Building, The Pennsylvania State University, University Park, PA 16802. Phone: (814)865-8091; Fax: (814) 863-0490; E-mail: cxd23@psu.edu

Molecular & Cellular Biomechanics 2010, 7(2), 77-91. https://doi.org/10.3970/mcb.2010.007.077

Abstract

To complete the metastatic journey, cancer cells have to disseminate through the circulation and extravasate to distal organs. However, the extravasation process, by which tumor cells leave a blood vessel and invade the surrounding tissue from the microcirculation, remains poorly understood at the molecular level. In this study, tumor cell adhesion to the endothelium (EC) and subsequent extravasation were investigated under various flow conditions. Results have shown polymorphonuclear neutrophils (PMNs) facilitate melanoma cell adhesion to the EC and subsequent extravasation by a shear-rate dependent mechanism. Melanoma cell-PMN interactions are mediated by the binding between intercellular adhesion molecule-1 (ICAM-1) on melanoma cells andb2integrins on PMNs. In addition, the fluid convection affects the extent of activation ofb2integrins on PMNs by endogenously secreted interleukin 8 (IL-8) within the tumor microenvironment. Results also indicate that shear rate affects the binding kinetics between PMNs and melanoma cells, which may contribute to the shear-rate dependence of melanoma extravasation in a shear flow when mediated by PMNs.

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