Abstract
Cell adhesion and motility are central aspects in the pathophysiology of B cell chronic lymphocytic leukemia (B-CLL), but the role of specific extracellular matrix proteins is still to be completely unveiled. Purified peripheral blood neoplastic cells of B-CLL patients migrated poorly on laminins-111,-411,-511, but showed pronounced motility on laminin (LM)-332 in a high percentage of cases. B-CLL cell motility on LM-332 was mediated by the alpha3beta1 integrin and was preferentially observed in cells carrying a mutated IgV(H) gene profile. Within normal lymph nodes, LM-332 was circumscribed around blood vessels and to areas corresponding to marginal zones, where it was deposited in a pattern reminiscent of reticular fibers. Conversely, in B-CLL involved lymph nodes, a positive LM-332 reticular mesh was diffusely evident, throughout the disrupted nodal architecture. In the present study we identified LM-332 as a crucial motility-promoting factor for B-CLL lymphocytes and as a potential constituent favoring the dissemination of B-CLL lymphocytes through vascular basement membranes and possibly lymph node compartments.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Aged
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Aged, 80 and over
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Antibodies, Monoclonal / pharmacology
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Cell Adhesion Molecules / genetics
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Cell Adhesion Molecules / metabolism
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Cell Adhesion Molecules / physiology*
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Cell Movement / drug effects
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Cell Movement / physiology*
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Female
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Fibronectins / metabolism
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Gene Expression
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Humans
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Immunoglobulin Heavy Chains / genetics
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Immunoglobulin Variable Region / genetics
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Immunohistochemistry
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Integrin alpha3beta1 / genetics
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Integrin alpha3beta1 / immunology
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Integrin alpha3beta1 / metabolism
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Kalinin
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Leukemia, Lymphocytic, Chronic, B-Cell / genetics
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Leukemia, Lymphocytic, Chronic, B-Cell / metabolism
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Leukemia, Lymphocytic, Chronic, B-Cell / pathology*
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Lymph Nodes / metabolism
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Male
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Matrix Metalloproteinase 2 / genetics
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Matrix Metalloproteinase 2 / metabolism
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Matrix Metalloproteinase 9 / genetics
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Matrix Metalloproteinase 9 / metabolism
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Middle Aged
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Mutation
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Protein Isoforms / genetics
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Protein Isoforms / metabolism
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Protein Isoforms / physiology
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
Substances
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Antibodies, Monoclonal
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Cell Adhesion Molecules
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Fibronectins
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Immunoglobulin Heavy Chains
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Immunoglobulin Variable Region
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Integrin alpha3beta1
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Protein Isoforms
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RNA, Messenger
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Matrix Metalloproteinase 2
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Matrix Metalloproteinase 9