Abstract
Wnts comprise a family of secreted proteins that interact with receptors consisting of a Frizzled (Fz) family member alone or complexed with LDL receptor-related proteins (LRP5/6). Wnt signaling plays a crucial role in both development and differentiation, and activation of a 'canonical' Wnt pathway resulting in beta-catenin stabilization is associated with several types of human cancers. To date, little is known about potential Wnt signaling in mature lymphocytes or lymphoid neoplasia. Herein, we have analysed Wnt signaling in mature B cells (lymphomas) and plasma cells (multiple myeloma). Both Fz and LRP5/6 mRNAs were expressed in myeloma lines, but LRP5/6 were not observed in lymphomas. In myelomas, a canonical Wnt signaling pathway was activated following treatment with Wnt-3a as assessed by accumulation of beta-catenin, but beta-catenin levels actually decreased in lymphoma cells. Wnt-3a treatment further led to striking morphological changes in myeloma cells accompanied by rearrangement of the actin cytoskeleton. Morphological changes were associated with a second Wnt pathway dependent on Rho activation. These results suggest that Wnt responsiveness is a stage-specific phenomenon in B-cell development and that the morphological changes associated with Wnt signaling may play a role in the motility and metastatic potential of myeloma cells.
MeSH terms
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Actins / drug effects
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Actins / metabolism
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Actins / ultrastructure
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Adaptor Proteins, Signal Transducing
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B-Lymphocytes / drug effects
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B-Lymphocytes / metabolism
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Cell Lineage
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Cytoskeletal Proteins / metabolism
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DNA-Binding Proteins / metabolism
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Dishevelled Proteins
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Frizzled Receptors
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Glycoproteins / metabolism
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Humans
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Intercellular Signaling Peptides and Proteins
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Intracellular Signaling Peptides and Proteins
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LDL-Receptor Related Proteins
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Low Density Lipoprotein Receptor-Related Protein-5
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Low Density Lipoprotein Receptor-Related Protein-6
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Lymphoma, B-Cell / drug therapy
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Lymphoma, B-Cell / metabolism*
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Multiple Myeloma / metabolism
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Phosphoproteins
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Phosphorylation
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Proteins / drug effects
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Proteins / metabolism*
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Proteins / pharmacology
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Receptors, Cell Surface / genetics
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Receptors, Cell Surface / metabolism
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Receptors, G-Protein-Coupled*
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Receptors, LDL / genetics
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Receptors, LDL / metabolism
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Saccharomyces cerevisiae Proteins*
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Signal Transduction
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Trans-Activators / metabolism
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Wnt Proteins
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Wnt3 Protein
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Wnt3A Protein
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beta Catenin
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rhoA GTP-Binding Protein / metabolism
Substances
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Actins
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Adaptor Proteins, Signal Transducing
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CTNNB1 protein, human
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Cytoskeletal Proteins
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DKK1 protein, human
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DKK2 protein, human
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DNA-Binding Proteins
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Dishevelled Proteins
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Dkk1 protein, mouse
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FZD3 protein, human
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Frizzled Receptors
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Fzd3 protein, mouse
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Glycoproteins
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Intercellular Signaling Peptides and Proteins
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Intracellular Signaling Peptides and Proteins
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LDL-Receptor Related Proteins
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LIF1 protein, S cerevisiae
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LRP5 protein, human
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LRP6 protein, human
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Low Density Lipoprotein Receptor-Related Protein-5
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Low Density Lipoprotein Receptor-Related Protein-6
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Lrp5 protein, mouse
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Lrp6 protein, mouse
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Phosphoproteins
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Proteins
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Receptors, Cell Surface
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Receptors, G-Protein-Coupled
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Receptors, LDL
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Saccharomyces cerevisiae Proteins
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Trans-Activators
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WD repeat containing planar cell polarity effector
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WNT3A protein, human
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Wnt Proteins
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Wnt3 Protein
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Wnt3A Protein
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Wnt3a protein, mouse
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beta Catenin
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rhoA GTP-Binding Protein