Publications

Here is a selection of publications where different laminin isoforms are being used to create more authentic cell culture systems

  • Area of interest

  • Characterization of a conduit system containing laminin-5 in the human thymus: a potential transport system for small molecules

    Drumea-Mirancea M., Wessels J.T., Müller C.A., Essl M., Eble J.A., Tolosa E., Koch M., Reinhardt D.P., Sixt M., Sorokin L., Stierhof Y-D., Schwarz H., Klein G.
    Journal of Cell Science, 2006

    T cells develop in the thymus in a highly specialized cellular and extracellular microenvironment. Laminin-332 is predominantly found in the medulla of the human thymic lobules. Here, the authors show that laminin-332 is localized in a bi-membranous conduit-like structure, together with matrix components, such as collagen type IV, nidogen, perlecan, fibrillin-1 or -2, tenascin-C or fibrillar collagen types. 3D confocal microscopy suggested a tubular structure, whereas immunoelectron and transmission electron microscopy showed that the core of these tubes contained fibrillar collagens enwrapped by the laminin-332-containing membrane. These medullary conduits are surrounded by thymic epithelial cells, which in vitro were found to bind laminin-332. Dendritic cells were also detected in close vicinity to the conduits.

  • Laminins affect T cell trafficking and allograft fate

    Warren K.J., Iwami D., Harris D.G, Bromberg J.S., Burrell B.E.The Journal of Clinical Investigation, 2014

    Lymph nodes (LNs) are integral sites for the generation of immune tolerance and migration of CD4+ T cells, and induction of T-regs. Extracellular matrix proteins formed regions within the LN that were permissive for co-localization of alloantigen-presenting cells, alloreactive T cells, and T-regs. Laminin-411 is produced by vascular endothelial and promotes T cell migration. Laminin-511 and laminin-521 are also present in the endothelial basement membrane. However, laminin-511 and fails to promote T cell migration, although T cell co-stimulatory properties have been reported. Here they identified unique expression patterns of laminin proteins that correlated with alloantigen-specific immunity or immune tolerance in mice. Laminin α4 (R&D Systems Inc.) and LN-511 were used for in vitro experiments. The ratio of laminin α4 to laminin α5 was greater in domains within tolerant LNs, compared with immune LNs, and blocking laminin α4 function or inducing laminin α5 overexpression disrupted T cell and dendritic cells localization These data again were commensurate with the in vitro migration results whereby laminin α5 impeded while α4 permitted migration through the endothelium and associated basement membrane. Furthermore, reducing α4 laminin circumvented tolerance induction and induced cardiac allograft inflammation and rejection in murine models. This work identifies laminins as potential targets for immune modulation.

  • Laminin chains in the basement membranes of human thymus

    Virtanen I., Lohi J., Tani T., Sariola H., Burgeson R.E., Lehto V-P Histochemical Journal, 1996

    The laminin a2 chain has been suggested to be the only laminin a chain expressed in mouse and human thymus. Here, the authors use monoclonal antibodies to study the expression of laminin chains in samples of fetal and 6-year-old human thymus. The subepithelial basement membrane of the capsule of fetal 16- to 18-week thymus presented a bright immunoreactivity for laminin a1, a3, B1, B3 and g1 chains but not for a2 chain, suggesting the expression of laminin-111 and -332. Most cortical and medullary epithelial cells, including Hassall's corpuscles, however, lacked laminin immunoreactivity. In thymic specimens from 6-year-old children, immunoreactivity for the laminin a1, a3, B1, B3 and g1 chains were invariably found in the subepithelial basement membrane of the capsule and that for laminin a2 chain was now also distinct but more heterogeneous. The present results show that the thymic subepithelial basement membrane of the capsule presents properties that are commonly seen in stratified and combined epithelia, and are compatible with suggestions of the antigenic similarity of thymic epithelial cells and keratinocytes.

  • Laminin-211 controls thymocyte—thymic epithelial cell interactions

    Laminin-211 controls thymocyte—thymic epithelial cell interactions

    Ocampo J.S.P., de Brito J.M,  Corrêa-de-Santana E., Borojevic R., Serra Villa-Verde D.M., Savino W.
    Cellular Immunology, 2008

    Thymocyte differentiation occurs within the thymic microenvironment. Previous experiments showed that laminin mediates interactions between thymocytes and thymic epithelial cells (TEC) in mice. Here, the authors show constitutive gene expression of various laminin chains in TEC preparations, comprising laminin-111 and laminin-211 isoforms. Immunocytochemistry revealed a selective laminin-211 distribution in the thymic lobules. In vitro, functional assays revealed that laminin-211 enhances TEC/thymocyte adhesion and thymocyte release from thymic nurse cells, as well as the reconstitution of these complexes. Conversely, these interactions are blocked by monoclonal antibodies specific for laminin-211 and the laminin receptor VLA-6. The results show that distinct laminin isoforms in the human thymus are relevant for lymphoepithelial interactions.

  • Laminin-Mediated Interactions in Thymocyte Migration and Development

    Savino W., Mendes-da-Cruz D.A., Golbert D.C., Riederer I., Cotta-de-Almeida V.Front Immunol., 2015

    In this review, the authors highlight the role of laminin isoforms for intrathymic T-cell migration and maturation in both physiological and pathological conditions. Intrathymic T-cell differentiation is a key process for the development and maintenance of cell-mediated immunity. Here, the authors propose a multivectorial model for describing intrathymic thymocyte migration. One of the individual vectors comprises interactions mediated by laminins. Several different laminin isoforms are expressed in the thymus, produced mainly by thymic epithelial cells (TECs). Thymocytes and epithelial cells express integrin-type laminin receptors. It has been reported that a mutant mouse that lack laminin-211 exhibits defective thymocyte differentiation. Several data also show haptotactic effects of laminin upon thymocytes and their adhesion on TECs. Interestingly, laminin synergizes with chemokines to enhance thymocyte migration. More recently, the authors show that knocking down the ITGA6 gene (which encodes the α6 integrin chain of laminin receptors) in human TECs modulates a large number of cell migration-related genes and results in changes of adhesion pattern of thymocytes into the thymic epithelium. Overall, laminin-mediated interactions can be placed at the cross-road of the multivectorial process of thymocyte migration, with a direct influence per se, as well as by modulating other molecular interactions associated with the intrathymic-trafficking events.

  • Human Mesenchymal Cells from Adipose Tissue Deposit Laminin and Promote Regeneration of Injured Spinal Cord in Rats

    Menezes K., Nascimento M.A., Goncalves J.P., Silva Cruz A., Vieira Lopes D., Curzio B., Bonamino M., Ricardo J., de Menezes L., Borojevic R., Doria Rossi M.I., Coelho-Sampaio T. PLoS ONE, 2013

    In this article, regenerative properties of human adipose tissue derived stromal cells (hADSCs) were investigated in a rat model of spinal cord compression. hADSCs were shown to secrete laminin in the spinal cord. Out of six isoforms tested, they confirmed expression of α2 and α5 and also found positivity for β2 and γ1 laminin chains. The authors propose that laminin can be the paracrine factor mediating the pro-regenerative effects of hADSCs in spinal cord injury. This is supposedly the first article in which a link between laminin and the pro-regenerative effects of mesenchymal cells in the central nervous system is proposed.

  • Differentiation-dependent Expression of Laminin-8 (α4β1γ1) mRNAs in Mouse 3T3-L1 Adipocytes

    Niimi T., Kumagai C., Okano M., Kitagaw Y.Matrix Biology, 1997

    Here, the authors report that laminin-411 is the specific isoform of laminin synthesized in adipocytes. Reverse transcription-polymerase chain reaction (RT-PCR) of mRNA from mouse 3T3-L1 cells yielded amplified fragments only for α4β1γ1. Northern blots showed that the levels of α4,β1, and γ1 mRNAs increased 2.5-fold during adipose conversion of 3T3-L1 cells. A 1062 bp cDNA fragment cloned by RT-PCR demonstrated a polymorphism in the mouse a4 gene which would lead to five amino acid changes in the domain G.

  • Laminin a4 Deficient Mice Exhibit Decreased Capacity for Adipose Tissue Expansion and Weight Gain

    Vaicik M.K., Thyboll Kortesmaa J., Movérare-Skrtic S., Kortesmaa J., Soininen R., Bergström G., Ohlsson C., Chong L.Y., Rozell B., Emont M., Cohen R.N., Brey E.M., Tryggvason K.PLOS ONE, 2014

    Staining was performed for known adipose tissue BM proteins. In wild-type control mice the a2 and a4 chains of laminin were present in the BM surrounding mature adipocytes. Laminin a5 was not observed in mouse adipocyte BM. In this manuscript, we describe the role of laminin a4, a specialized ECM protein surrounding adipocytes, on weight gain and adipose tissue function. Adipose tissue accumulation, lipogenesis, and structure were examined in mice with a null mutation of the laminin a4 gene (Lama42/2) and compared to wild-type (Lama4+/+) control animals. Lama42/2 mice exhibited reduced weight gain in response to both age and high-fat diet. Interestingly, the mice had decreased adipose tissue mass and altered lipogenesis in a depot-specific manner. In particular, epididymal adipose tissue mass was specifically decreased in knock-out mice, and there was also a defect in lipogenesis in this depot as well. In contrast, no such differences were observed in subcutaneous adipose tissue at 14 weeks. The results suggest that laminin a4 influences adipose tissue structure and function in a depot-specific manner.

  • Cell–Matrix Interactions in Mammary Gland Development and Breast Cancer

    Muschler J., Streuli C.H.Cold Spring Harb Perspect Biol., 2010

    Here, the authors argue that the interactions between mammary epithelial cells and their extracellular matrix (ECM) are crucial in the development and function of the tissue. Current strategies for treating breast cancer take advantage of our knowledge of the endocrine regulation and stromal–epithelial interactions. In addition, focusing on the microenvironmental influences that arise from cell-matrix interactions may open new opportunities for therapeutic intervention, suggesting a treatment where endocrine, growth factor, and cell-matrix interactions are targeted.

  • Regulation of mammary gland branching morphogenesis by the extracellular matrix and its remodeling enzymes

    Fata J.E., Werb Z. Bissell M.JBreast Cancer Res 2004

    A considerable body of research indicates that mammary gland branching morphogenesis is dependent, in part, on the extracellular matrix, affecting cell survival, polarity, proliferation, differentiation, adhesion, and migration. However, the precise mechanisms of ECM-directed mammary morphogenesis are not well understood and is discussed in this review. Mammary morphogenesis involves epithelial invasion of adipose tissue, a process akin to invasion by breast cancer cells, although the former is a highly regulated developmental process. How these morphogenic pathways are integrated into the normal gland and how they become dysregulated and subverted in the progression of breast cancer also remain largely unanswered questions.