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Perspectives: Interplay Between Melanoma Regulated Fibrin and Receptor Mediated Adhesion Under Shear Flow

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Abstract

Metastasis is a complex process that ultimately results in secondary tumor formation, posing a threat to patient survival. However, the mechanisms by which circulating tumor cells adhere to the endothelium and escape from the vasculature are not fully understood. To bind to the endothelium, tumor cells must resist the shear forces induced by flow, largely through receptor-mediated cell–cell interactions. Tumor cells are able to manipulate the metastatic site microenvironment via thrombin and soluble fibrin (sFn) regulation, impacting both coagulation and cell adhesion processes. Thus, thrombosis may be recognized as a prognostic indicator of highly metastatic tumors. Herein, we describe some correlations between the metastatic potential of tumor cells and coagulation. This perspectives review focuses on the role of sFn in melanoma-endothelial adhesions under shear conditions. Specifically, sFn serves as a divalent ligand for αvβ3, CD11b/CD18 (αmβ2, Mac-1), and intercellular adhesion molecule-1 (ICAM-1) transmembrane receptors. The cross-linking role of sFn is examined in relation to host leukocytes, in particular, the polymorphonuclear neutrophil (PMN)-mediated adhesions of melanoma cells to the endothelium. These results have shed light on the significant interplay between melanoma cells, PMNs, and the endothelium under shear conditions, which is key in the struggle to better diagnose and treat melanoma metastases.

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Acknowledgments

We thank Dr. Erwin Vogler for use of his facilities in performing coagulation experiments. Additionally, we thank Dr. Scott I. Simon (UC Davis) for kindly providing EI cells; Dr. Meenhard Herlyn (The Wistar Institute Melanoma Research Center) for providing WM35 melanoma cells; Dr. Gavin Robertson (Penn State Hershey Medical Center) for Lu1205 melanoma cells. We also thank Virginia Aragon-Sanabria and David Gaddes for critically reading the manuscript. This study was partially funded by NIH (CA-125707), NSF (CBET-0729091), NSF (CBET-1330663), and NSF (CBET- 1340173).

Conflict of interest

T Ozdemir, E. Gaddes, Y. Wang, and C. Dong declare that they have no conflicts of interest.

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No human or animal studies were carried out by the authors for this article.

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Authors and Affiliations

  1. Department of Biomedical Engineering, The Pennsylvania State University, University Park, PA, 16802, USA

    Tugba Ozdemir, Erin Gaddes, Yong Wang & Cheng Dong

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  1. Tugba Ozdemir
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Correspondence to Cheng Dong.

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Associate Editor Edward Sander oversaw the review of this article.

Tugba Ozdemir and Erin Gaddes are equal first authors.

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Ozdemir, T., Gaddes, E., Wang, Y. et al. Perspectives: Interplay Between Melanoma Regulated Fibrin and Receptor Mediated Adhesion Under Shear Flow. Cel. Mol. Bioeng. 8, 86–95 (2015). https://doi.org/10.1007/s12195-014-0369-0

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