Endoglin is a component of the transforming growth factor (TGF)-beta receptor complex of human pre-B leukemic cells.
Endoglin was first identified on a cell line derived from pre-B acute lymphoblastic leukemia. This 180-kDa homodimeric glycoprotein was then shown to be primarily expressed on endothelial cells and to bind the beta 1 and beta 3 isoforms of TGF-beta with high affinity. We now demonstrate that pre-B leukemic cells express a functional TGF-beta 1 receptor complex. The levels of mRNA for these receptors and for TGF-beta 1 were quantitated by PCR. HOON, G2, and NALM-6 cell lines express similar levels of mRNA for TGF-beta 1 and for TGF-beta receptor I (R-I) and receptor II (R-II). HOON cells express ten times more endoglin than G2 and NALM-6 cells, whereas all three cell lines have low levels of betaglycan relative to other cell types. The receptors were identified by affinity labeling with 125I-labeled TGF-beta 1, chemical cross-linking, and specific immunoprecipitation. Endoglin, R-II, and R-I were co-precipitated by Abs to either endoglin or R-II, indicating that these proteins are forming a receptor complex on leukemic cells; no betaglycan could be immunoprecipitated. The receptor complex is functional, as demonstrated by inhibition of proliferation of HOON cells (80%) and NALM-6 cells (60%) with 25 pM TGF-beta 1. Furthermore, the motility of HOON and NALM-6 cells on immobilized fibronectin, which appears to be alpha 4 beta 1-integrin mediated, was stimulated two- to threefold by TGF-beta 1. These results suggest that active TGF-beta 1 produced in the bone marrow microenvironment might stimulate the motility of normal pre-B cells and the peripheral dissemination of leukemic pre-B cells.
Division of Immunology and Cancer Research, Hospital for Sick Children, Toronto, Canada.
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D030201:Activin Receptors, Type I; D015703:Antigens, CD; D001483:Base Sequence; D002455:Cell Division; D002465:Cell Movement / Q000187:drug effects; D000071063:Endoglin; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism* / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics; D011509:Proteoglycans / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D014407:Tumor Cells, Cultured; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics
D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D046911:Macromolecular Substances; D009363:Neoplasm Proteins; D011509:Proteoglycans; D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D019010:Vascular Cell Adhesion Molecule-1; C071736:betaglycan; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II