Abstract
Metastastic tumor cells must form stable adhesive contacts with microvascular elements in target organs. The interactions at the vessel wall are complex and may vary depending on the cells involved. We have developed hydrodynamic assays that mimic conditions in the microcirculation to study metastatic tumor cell interactions with endothelial cells and their underlying extracellular matrix. Acquisition and analysis of data are computerized, enabling us to distinguish the primary events of arrest from secondary events of adhesion stabilization. Using this system we have determined that initial receptor-ligand interactions do not effectively maintain prolonged adhesive contacts unless followed by adhesion stabilization. We have examined tumor cell lines that were derived from different developmental origins and malignant potentials and observed differences in their adhesion stabilization behavior. The adhesion behaviors of human metastatic melanoma cells that originate from the neuroepithelium (MeWo, 3S5, and 70W cells) are quite different from murine large-cell lymphoma cells that arise from mesothelia (RAW117-P, -L17, and -H10). Melanoma cells adhered to many extracellular matrix proteins or RGD peptides but large-cell lymphoma cells responded to a more limited repertoire of components. Melanoma cells express a variety of integrins compared to the more limited integrin profiles expressed by large-cell lymphoma cells, and melanoma cells were more highly responsive and spread more fully under laminar flow than the limited spreading and slow adhesion stabilization of large-cell lymphoma cells. The adhesion stabilization properties of these tumor cells correlated with their metastatic properties; melanoma cells typically metastasize to a variety of organ sites compared to the organ preferential targeting of large-cell lymphoma cells. These methods measure dynamic responses of tumor cell and we conclude that these hydrodynamic analysis methods are highly sensitive and reflective of metastatic behavior.
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Menter, D.G., Smith, T.W., Yun, Z., Patton, J., McIntire, L.V., Nicolson, G.L. (1996). Adhesion Stabilization of Blood Borne Cancer Cells in the Microcirculation. In: Kohen, E., Hirschberg, J.G. (eds) Analytical Use of Fluorescent Probes in Oncology. NATO ASI Series, vol 286. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5845-3_14
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DOI: https://doi.org/10.1007/978-1-4615-5845-3_14
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