title: Selectin-deficiency reduces the number of spontaneous metastases in a xenograft model of human breast cancer.
abstract: Metastasis formation is a complex process still poorly understood. Previous work in a colon cancer xenograft model showed that E(ndothelial) and P(latelet) selectins mediate spontaneous metastasis to the lungs. To investigate the functional role of selectins in breast cancer, human DU4475 breast cancer cells were injected subcutaneously into pfp-/-rag2-/- mice and in all their selectin-deficient variants (EP-/-, E-/- and P-/-). Pfp-/-rag2-/- mice as well as all their selectin-deficient variants developed primary tumours and spontaneous metastases. Compared with the wild-type mice, disseminated tumours cells were significantly lower (74% reduction, P=0.046) in the bone marrow of selectin-deficient mice. Pfp-/-rag2-/- mice developed significantly higher numbers of lung metastases (6644.83±741.77) than the E-/- (4053.33±112.58; P=0.002) and the EP-/- pfp-/-rag2-/- mice (4665.65±754.50; P<0.001). The results indicate that E- and P-selectins play a role in spontaneous metastasis formation both into bone marrow and lungs. However, spontaneous metastasis was not completely abrogated, hence additional cell adhesion molecules must be involved in the metastatic spread.
authors.affiliation: University Medical Center Hamburg-Eppendorf, Center for Experimental Medicine, Department of Anatomy and Experimental Morphology, Hamburg, Germany. katrin.stuebke@med.uni-duesseldorf.de
authors.forename: Katrin
authors.initials: K
authors.lastname: Stübke
authors.forename: Daniel
authors.initials: D
authors.lastname: Wicklein
authors.forename: Lena
authors.initials: L
authors.lastname: Herich
authors.forename: Udo
authors.initials: U
authors.lastname: Schumacher
authors.forename: Nina
authors.initials: N
authors.lastname: Nehmann
mesh_terms: D000818:Animals; D019046:Bone Marrow Neoplasms / Q000556:secondary*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D019040:E-Selectin / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000556:secondary*; D051379:Mice; D018345:Mice, Knockout; D019007:P-Selectin / Q000378:metabolism*; D014183:Transplantation, Heterologous
chemical_list: D019040:E-Selectin; D019007:P-Selectin; C546937:SELP protein, human