Abstract
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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Activin Receptors, Type I*
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Antigens, CD
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Base Sequence
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Cell Division
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Cell Movement / drug effects
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Endoglin
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Gene Expression Regulation, Leukemic
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Humans
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Macromolecular Substances
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Molecular Sequence Data
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Neoplasm Proteins / biosynthesis
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Neoplasm Proteins / chemistry*
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Neoplasm Proteins / genetics
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Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / metabolism*
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Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / pathology
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Protein Serine-Threonine Kinases / biosynthesis
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Protein Serine-Threonine Kinases / chemistry*
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Protein Serine-Threonine Kinases / genetics
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Proteoglycans / biosynthesis
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Proteoglycans / chemistry*
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Proteoglycans / genetics
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Receptor, Transforming Growth Factor-beta Type I
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Receptor, Transforming Growth Factor-beta Type II
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Receptors, Cell Surface
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Receptors, Transforming Growth Factor beta / biosynthesis
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Receptors, Transforming Growth Factor beta / chemistry*
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Receptors, Transforming Growth Factor beta / genetics
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Signal Transduction
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Transforming Growth Factor beta / biosynthesis
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Transforming Growth Factor beta / genetics
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Transforming Growth Factor beta / pharmacology
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Transforming Growth Factor beta / physiology*
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Tumor Cells, Cultured
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Vascular Cell Adhesion Molecule-1 / analysis*
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Vascular Cell Adhesion Molecule-1 / biosynthesis
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Vascular Cell Adhesion Molecule-1 / genetics
Substances
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Antigens, CD
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ENG protein, human
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Endoglin
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Macromolecular Substances
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Neoplasm Proteins
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Proteoglycans
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Receptors, Cell Surface
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Receptors, Transforming Growth Factor beta
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Transforming Growth Factor beta
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Vascular Cell Adhesion Molecule-1
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betaglycan
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Protein Serine-Threonine Kinases
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Activin Receptors, Type I
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Receptor, Transforming Growth Factor-beta Type I
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Receptor, Transforming Growth Factor-beta Type II