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Effects of the Tumor-Leukocyte Microenvironment on Melanoma–Neutrophil Adhesion to the Endothelium in a Shear Flow

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Abstract

The primary cause of cancer mortality is not attributed to primary tumor formation, but rather to the growth of metastases at distant organ sites. Tumor cell adhesion to blood vessel endothelium (EC) and subsequent transendothelial migration within the circulation are critical components of the metastasis cascade. Previous studies have shown polymorphonuclear neutrophils (PMNs) may facilitate melanoma cell adhesion to the EC and subsequent extravasation under flow conditions. The melanoma cell–PMN interactions are found to be mediated by the binding between intercellular adhesion molecule-1 (ICAM-1) on melanoma cells and β2 integrin on PMNs and by endogenously secreted interleukin 8 (IL-8) within the tumor-leukocyte microenvironment. In this study, the effects of fluid convection on the IL-8-mediated activation of PMNs and the binding kinetics between PMNs and melanoma cells were investigated. Results indicate that the shear rate dependence of PMN–melanoma cell adhesion and melanoma cell extravasation is due, at least partly, to the convection of tumor-secreted proinflammatory cytokine IL-8.

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Acknowledgments

The authors thank Dr. Scott Simon (UC Davis, CA) for providing EI cells and Dr. Meenhard Herlyn (Wistar Institute, Philadelphia, PA) for providing WM9 cells. This work was supported by the National Institutes of Health grant CA-97306, CA-125707 and National Science Foundation grant CBET-0729091. The authors acknowledge and appreciate complimentary software licenses provided to the authors by CEI, Inc. (Harpoon and Ensight) and ACUSIM Software, Inc. (AcuSolve). The authors appreciate the support of the Pennsylvania State University Applied Research Laboratory and Penn State General Clinical Research Center (GCRC), the staff that provided nursing care. The GCRC is supported by NIH Grant M01-RR-10732.

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Authors and Affiliations

  1. Department of Bioengineering, The Pennsylvania State University, 233 Hallowell Building, University Park, PA, 16802, USA

    Shile Liang, Meghan Hoskins, Payal Khanna & Cheng Dong

  2. Applied Research Laboratory, The Pennsylvania State University, University Park, PA, 16802, USA

    Meghan Hoskins & Robert F. Kunz

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  1. Shile Liang
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  2. Meghan Hoskins
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  3. Payal Khanna
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  4. Robert F. Kunz
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  5. Cheng Dong
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Corresponding author

Correspondence to Cheng Dong.

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Shile Liang and Meghan Hoskins contributed equivalently to this work.

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Liang, S., Hoskins, M., Khanna, P. et al. Effects of the Tumor-Leukocyte Microenvironment on Melanoma–Neutrophil Adhesion to the Endothelium in a Shear Flow. Cel. Mol. Bioeng. 1, 189–200 (2008). https://doi.org/10.1007/s12195-008-0016-8

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  • DOI: https://doi.org/10.1007/s12195-008-0016-8

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