title: Adhesion of small cell lung cancer cells to E- and P-selectin under physiological flow conditions: implications for metastasis formation.
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.
authors.affiliation: Institute for Anatomy II: Experimental Morphology, University Cancer Center, University Medical Center Hamburg Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany. Ulrich.Richter@law-school.de
authors.forename: Ulrich
authors.initials: U
authors.lastname: Richter
authors.forename: Christine
authors.initials: C
authors.lastname: Schröder
authors.forename: Daniel
authors.initials: D
authors.lastname: Wicklein
authors.forename: Tobias
authors.initials: T
authors.lastname: Lange
authors.forename: Silvana
authors.initials: S
authors.lastname: Geleff
authors.forename: Virginia
authors.initials: V
authors.lastname: Dippel
authors.forename: Udo
authors.initials: U
authors.lastname: Schumacher
authors.forename: Susanne
authors.initials: S
authors.lastname: Klutmann
mesh_terms: D002448:Cell Adhesion; D019040:E-Selectin / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000473:pathology*; D009362:Neoplasm Metastasis / Q000473:pathology*; D019007:P-Selectin / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D055752:Small Cell Lung Carcinoma / Q000473:pathology*; D014407:Tumor Cells, Cultured
chemical_list: D019040:E-Selectin; D019007:P-Selectin; D011994:Recombinant Proteins