Abstract
Haematogenous metastasis of small cell lung cancer (SCLC) is still a poorly understood process and represents the life threatening event in this malignancy. In particular, the rate-limiting step within the metastatic cascade is not yet clearly defined although, many findings indicate, that extravasation of circulating tumour cells is crucially important as most tumour cells within the circulation undergo apoptosis. If extravasation of SCLC tumour cells mimics leukocyte–endothelial interactions, SCLC cells should adhere to E- and P-selectins expressed on the luminal surface of activated endothelium. The adhesion to E- and P-selectin under physiological shear stress with regard to adhesive events, rolling behaviour and rolling velocity was determined in the human SCLC cell lines SW2, H69, H82, OH1 and OH3. OH1 SCLC cells adhered best to recombinant human (rh) E-selectin FC-chimeras and human lung endothelial cells (HPMEC), H82 SCLC cells adhered best to activated human umbilical vein endothelial cells (HUVEC) under physiological shear stress. As OH1 cells had also produced by far the highest number of spontaneous lung metastases when xenografted into pfp/rag2 mice in previous experiments our findings implicate that adhesion of SCLC cells to E-selectin is of paramount importance in SCLC metastasis formation.
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Acknowledgments
The authors thank PD Dr. med. Rainer Kiefmann and Dr. Martina Kiefmann for contributing lung endothelial cells, Julia Kemmling and Maike Märker for excellent help with the experiments, Renate Gehrcke and Klaus Siebert for excellent help with cell culture and Susanne Feldhaus for logistic support. U. R. is supported by a grant from the Werner Otto Foundation.
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U. Richter and C. Schröder contributed equally to this work.
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Richter, U., Schröder, C., Wicklein, D. et al. Adhesion of small cell lung cancer cells to E- and P-Selectin under physiological flow conditions: implications for metastasis formation. Histochem Cell Biol 135, 499–512 (2011). https://doi.org/10.1007/s00418-011-0804-4
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DOI: https://doi.org/10.1007/s00418-011-0804-4