title: Laminin isoform-specific promotion of adhesion and migration of human bone marrow progenitor cells.
abstract: Laminins are alphabetagamma heterotrimeric extracellular proteins that regulate cellular functions by adhesion to integrin and nonintegrin receptors. Laminins containing alpha4 and alpha5 chains are expressed in bone marrow, but their interactions with hematopoietic progenitors are unknown. We studied human bone marrow cell adhesion to laminin-10/11 (alpha5beta1gamma1/alpha5beta2gamma1), laminin-8 (alpha4beta1gamma1), laminin-1 (alpha1beta1gamma1), and fibronectin. About 35% to 40% of CD34(+) and CD34(+)CD38(-) stem and progenitor cells adhered to laminin-10/11, and 45% to 50% adhered to fibronectin, whereas they adhered less to laminin-8 and laminin-1. Adhesion of CD34(+)CD38(-) cells to laminin-10/11 was maximal without integrin activation, whereas adhesion to other proteins was dependent on protein kinase C activation by 12-tetradecanoyl phorbol-13-acetate (TPA). Fluorescence-activated cell-sorting (FACS) analysis showed expression of integrin alpha6 chain on most CD34(+) and CD34(+)CD38(-) cells. Integrin alpha6 and beta1 chains were involved in binding of both cell fractions to laminin-10/11 and laminin-8. Laminin-10/11 was highly adhesive to lineage-committed myelomonocytic and erythroid progenitor cells and most lymphoid and myeloid cell lines studied, whereas laminin-8 was less adhesive. In functional assays, both laminin-8 and laminin-10/11 facilitated stromal-derived factor-1alpha (SDF-1alpha)-stimulated transmigration of CD34(+) cells, by an integrin alpha6 receptor-mediated mechanism. In conclusion, we demonstrate laminin isoform-specific adhesive interactions with human bone marrow stem, progenitor, and more differentiated cells. The cell-adhesive laminins affected migration of hematopoietic progenitors, suggesting a physiologic role for laminins during hematopoiesis.
authors.affiliation: Department of Medical Biochemistry and Biophysics, Karolinska Institute and BioStratum AB, Stockholm, Sweden.
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Gu
authors.forename: Jarkko
authors.initials: J
authors.lastname: Kortesmaa
authors.forename: Karl
authors.initials: K
authors.lastname: Tryggvason
authors.forename: Jenny
authors.initials: J
authors.lastname: Persson
authors.forename: Peter
authors.initials: P
authors.lastname: Ekblom
authors.forename: Sten-Eirik
authors.initials: SE
authors.lastname: Jacobsen
authors.forename: Marja
authors.initials: M
authors.lastname: Ekblom
mesh_terms: D018952:Antigens, CD34; D001854:Bone Marrow Cells / Q000166:cytology*; D002448:Cell Adhesion; D002465:Cell Movement; D005353:Fibronectins / Q000378:metabolism; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D007797:Laminin / Q000378:metabolism* / Q000502:physiology; D020033:Protein Isoforms / Q000378:metabolism / Q000502:physiology; D017474:Receptors, Laminin / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; D005353:Fibronectins; D007797:Laminin; D020033:Protein Isoforms; D017474:Receptors, Laminin; C121346:laminin 1; C119013:laminin 10; C110308:laminin 8