E- and p-selectins are essential for repopulation of chronic myelogenous and chronic eosinophilic leukemias in a scid mouse xenograft model
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E- and p-selectins are essential for repopulation of chronic myelogenous and chronic eosinophilic leukemias in a scid mouse xenograft model. / Wicklein, Daniel; Schmidt, Anna; Labitzky, Vera; Ullrich, Sebastian; Valent, Peter; Schumacher, Udo.
in: PLOS ONE, Jahrgang 8, Nr. 7, 01.01.2013, S. e70139.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - E- and p-selectins are essential for repopulation of chronic myelogenous and chronic eosinophilic leukemias in a scid mouse xenograft model
AU - Wicklein, Daniel
AU - Schmidt, Anna
AU - Labitzky, Vera
AU - Ullrich, Sebastian
AU - Valent, Peter
AU - Schumacher, Udo
PY - 2013/1/1
Y1 - 2013/1/1
N2 - In chronic myelogenous (CML) and chronic eosinophilic leukemia (CEL), neoplastic cells spread via the circulation into various extramedullary organs. As E- and P-selectin constitute the starting point for the leucocyte adhesion/invasion cascade, and CEL and CML cells share many properties with normal granulocytes, we investigated the role of these selectins in CEL and CML cell expansion and organ invasion in a xenotransplantation model using scid mice. Using two human leukemic cell lines (EOL-1 and K562), we were able to show that E- and P-selectins mediate leukemia cell tethering and adherence in a laminar flow assay. While E-selectin binding depended on sialylated carbohydrate moieties, P-selectin binding was completely (K562) or partially (EOL-1) independent of these carbohydrates indicating the involvement of non-canonical selectin ligands. In a xenograft model in scid mice, both cell lines invaded the bone marrow and other organs, formed chloromas, and ultimately produced an overt leukemia. In contrast, in E- and P-selectin knockout scid mice, the cells failed to show engraftment in 8 out of 10 animals and even if they did engraft, they produced only little organ invasion and chloroma formation. Together, these data suggest that E- and P-selectins play an important role in leukemic dissemination in CML and CEL.
AB - In chronic myelogenous (CML) and chronic eosinophilic leukemia (CEL), neoplastic cells spread via the circulation into various extramedullary organs. As E- and P-selectin constitute the starting point for the leucocyte adhesion/invasion cascade, and CEL and CML cells share many properties with normal granulocytes, we investigated the role of these selectins in CEL and CML cell expansion and organ invasion in a xenotransplantation model using scid mice. Using two human leukemic cell lines (EOL-1 and K562), we were able to show that E- and P-selectins mediate leukemia cell tethering and adherence in a laminar flow assay. While E-selectin binding depended on sialylated carbohydrate moieties, P-selectin binding was completely (K562) or partially (EOL-1) independent of these carbohydrates indicating the involvement of non-canonical selectin ligands. In a xenograft model in scid mice, both cell lines invaded the bone marrow and other organs, formed chloromas, and ultimately produced an overt leukemia. In contrast, in E- and P-selectin knockout scid mice, the cells failed to show engraftment in 8 out of 10 animals and even if they did engraft, they produced only little organ invasion and chloroma formation. Together, these data suggest that E- and P-selectins play an important role in leukemic dissemination in CML and CEL.
KW - Animals
KW - Cell Line, Tumor
KW - Disease Models, Animal
KW - E-Selectin
KW - Humans
KW - Hypereosinophilic Syndrome
KW - Leukemia, Myelogenous, Chronic, BCR-ABL Positive
KW - Mice
KW - Mice, Knockout
KW - Mice, SCID
KW - P-Selectin
KW - Transplantation, Heterologous
U2 - 10.1371/journal.pone.0070139
DO - 10.1371/journal.pone.0070139
M3 - SCORING: Journal article
C2 - 23922938
VL - 8
SP - e70139
JO - PLOS ONE
JF - PLOS ONE
SN - 1932-6203
IS - 7
ER -
