P-selectin mediates adhesion of platelets to neuroblastoma and small cell lung cancer.
Activated platelets and stimulated endothelial cells express P-selectin, an integral membrane protein receptor that binds monocytes and neutrophils. P-selectin mediates adhesion to glycoproteins with carbohydrate structures containing sialyl-Lewis X. Since many carcinoma cells also express these carbohydrate structures and are known to interact with platelets, we asked whether P-selectin may mediate this interaction. Both small cell lung cancer and neuroblastoma cell lines bound to activated platelets, and this interaction was blocked with inhibitory anti-P-selectin antibodies and by pretreatment of these cancer cells with neuraminidase or trypsin. Platelet binding to the small cell lung cancer cells was not inhibited with anti-GP IIb-IIIa antibody or Arg-Gly-Asp-Ser peptide. Pretreatment of the neuroblastoma cells with inhibitors of N-linked carbohydrate biosynthesis had little effect on binding to P-selectin, indicating that relevant carbohydrate ligand(s) may be O-linked. In addition, lipospheres containing P-selectin specifically bound to cryostat sections derived from a small cell lung tumor and two neuroblastoma tumors, but not to sections of normal lung. These observations demonstrate that P-selectin mediates binding of platelets to small cell lung cancer and to neuroblastoma and suggest a possible role for this lectin in metastasis.
Stone
J P
JP
Center for Hemostasis and Thrombosis Research, New England Medical Center 02111.
Wagner
D D
DD
D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000502:physiology*; D001792:Blood Platelets / Q000502:physiology*; D018288:Carcinoma, Small Cell / Q000503:physiopathology*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000502:physiology; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute; D008175:Lung Neoplasms / Q000503:physiopathology*; D016403:Lymphoma, Large B-Cell, Diffuse; D009447:Neuroblastoma / Q000503:physiopathology*; D019007:P-Selectin; D010743:Phospholipids / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins / Q000502:physiology*; D012397:Rosette Formation; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D019007:P-Selectin; D010743:Phospholipids; D010980:Platelet Membrane Glycoproteins