Adhesion of small cell lung cancer cells to E- and P-selectin under physiological flow conditions: implications for metastasis formation.
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Adhesion of small cell lung cancer cells to E- and P-selectin under physiological flow conditions: implications for metastasis formation. / Richter, Ulrich; Schröder, Christine; Wicklein, Daniel; Lange, Tobias; Geleff, Silvana; Dippel, Virginia; Schumacher, Udo; Klutmann, Susanne.
in: HISTOCHEM CELL BIOL, Jahrgang 135, Nr. 5, 5, 2011, S. 499-512.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Adhesion of small cell lung cancer cells to E- and P-selectin under physiological flow conditions: implications for metastasis formation.
AU - Richter, Ulrich
AU - Schröder, Christine
AU - Wicklein, Daniel
AU - Lange, Tobias
AU - Geleff, Silvana
AU - Dippel, Virginia
AU - Schumacher, Udo
AU - Klutmann, Susanne
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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.
KW - Humans
KW - Immunohistochemistry
KW - Flow Cytometry
KW - Tumor Cells, Cultured
KW - Cell Adhesion
KW - E-Selectin/metabolism
KW - Endothelial Cells/metabolism/pathology
KW - Lung Neoplasms/pathology
KW - Neoplasm Metastasis/pathology
KW - P-Selectin/metabolism
KW - Recombinant Proteins/metabolism
KW - Small Cell Lung Carcinoma/pathology
KW - Humans
KW - Immunohistochemistry
KW - Flow Cytometry
KW - Tumor Cells, Cultured
KW - Cell Adhesion
KW - E-Selectin/metabolism
KW - Endothelial Cells/metabolism/pathology
KW - Lung Neoplasms/pathology
KW - Neoplasm Metastasis/pathology
KW - P-Selectin/metabolism
KW - Recombinant Proteins/metabolism
KW - Small Cell Lung Carcinoma/pathology
M3 - SCORING: Journal article
VL - 135
SP - 499
EP - 512
JO - HISTOCHEM CELL BIOL
JF - HISTOCHEM CELL BIOL
SN - 0948-6143
IS - 5
M1 - 5
ER -