Oncotarget

Research Papers:

E-selectin ligand-1 controls circulating prostate cancer cell rolling/adhesion and metastasis

Sayeda Yasmin-Karim _, Michael R. King, Edward M. Messing and Yi-Fen Lee

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Oncotarget. 2014; 5:12097-12110. https://doi.org/10.18632/oncotarget.2503

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Abstract

Sayeda Yasmin-Karim1, Michael R. King2, Edward M. Messing1, Yi-Fen Lee1

1Departments of Urology and Pathology and Laboratory Medicine, and Chemical Engineering, University of Rochester, Rochester, NY 14642

2Department of Biomedical Engineering, Cornell University, Ithaca, NY 14853

Correspondence to:

Yi-Fen Lee, e-mail: [email protected]

Keywords: prostate cancer, circulatory tumor cell, cancer cell rolling and adhesion, E-selectin ligand-1, E-selectin

Received: July 31, 2014     Accepted: September 16, 2014     Published: October 06, 2014

ABSTRACT

Circulating prostate cancer (PCa) cells preferentially roll and adhere on bone marrow vascular endothelial cells, where abundant E-selectin and stromal cell-derived factor 1 (SDF-1) are expressed, subsequently initiating a cascade of activation events that eventually lead to the development of metastases. To elucidate the roles of circulating PCa cells’ rolling and adhesion behaviors in cancer metastases, we applied a dynamic cylindrical flow-based microchannel device that is coated with E-selectin and SDF-1, mimicking capillary endothelium. Using this device we captured a small fraction of rolling PCa cells. These rolling cells display higher static adhesion ability, more aggressive cancer phenotypes and stem-like properties. Importantly, mice received rolling PCa cells, but not floating PCa cells, developed cancer metastases. Genes coding for E-selectin ligands and genes associated with cancer stem cells and metastasis were elevated in rolling PCa cells. Knock down of E-selectin ligand 1(ESL-1), significantly impaired PCa cells’ rolling capacity and reduced cancer aggressiveness. Moreover, ESL-1 activates RAS and MAP kinase signal cascade, consequently inducing the downstream targets. In summary, circulating PCa cells’ rolling capacity contributes to PCa metastasis, and that is in part controlled by ESL-1.


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