Publications
Here is a selection of publications where different laminin isoforms were used to create more authentic cell culture systems.
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.
Endothelin A receptor activation on mesangial cells initiates Alport glomerular disease
Dufek B. Meehan D.T., Delimont D., Cheung L., Gratton M.A., Phillips G., Song W., Liu S., Cosgrove D.International Society of Nephrology, 2016
Normally, α5 laminins are highly expressed in the glomerular basement membranes (GBM). In this article, the authors show that the mesangial filopodia in the GBM are depositing mesangial matrix proteins, including laminin 211, which activates focal adhesion kinase in glomerular podocytes, resulting in the activation of genes encoding proinflammatory cytokines and metalloproteinases through a nuclear factor kB–dependent signaling pathway, which drive the progression of glomerulonephritis. The authors test whether endothelial cell-derived endothelin-1 is up-regulated in Alport glomeruli and further elevated by hypertension. Endothelin A receptor activation on mesangial cells is a key event in the initiation of Alport glomerular disease in this model.
Vascular laminins in physiology and pathology
Di Russo J., Hannocks M-J., Luik A-L., Song J., Zhang X., Yousif L., Aspite G., Hallmann R., Sorokin L. Matrix biology, 2016
Review on vascular laminins. In the healthy vessel, basement membranes (BMs) are the main ECM structures found in the vessel wall, underlying endothelium and surrounding vascular smooth muscle cells. Laminin α4 and α5 chains are the major α chains occurring in endothelial BMs and in vascular smooth muscle BMs. In most cases, laminins α4 and α5 combine with laminin β1 and γ1 chains to form laminins-411 and -511 in endothelial BMs; however, there is also evidence for the expression of laminin β2 in several tissues suggesting the additional existence of laminins-421 and -521 in endothelial BMs. While laminin α2 does not occur in endothelial BMs it can occur in association with perivascular cells including smooth muscle BMs of large arteries, such as the aorta, but not of smaller arterioles. There is no laminin α1 in endothelial or smooth muscle BMs regardless of tissue or species.
L1CAM defines the regenerative origin of metastasis-initiating cells in colorectal cancer
Ganesh K., Basnet H., Kaygusuz Y., Laughney A.M., He L., Sharma R., O’Rourke K.P., Reuter V.P., Huang Y.-H., Turkekul M., Er E.E., Masilionis I., Manova-Todorova K., Weiser M.R., Saltz L.B., Garcia-Aguilar J., Koche R., Lowe S.W., Pe’er D., Shia J., Massagué J.Nature Cancer, 2020
The authors show that L1CAM+ cells in human colorectal cancer (CRC) have metastasis-initiating capacity, and they define their relationship to tissue regeneration. By using recombinant L1CAM extracellular domain and basement membrane components, they confirmed that L1CAM bound heterophilically to laminins known to be expressed in the intestinal and endothelial cell basement membranes in addition to exhibiting homophilic interaction with L1CAM itself. L1CAM knockdown inhibited the ability of CRC organoid-derived cells to bind to laminin-coated plates. Together, these data suggest that L1CAM enables the adhesion of metastasis-initiating cells to laminin-rich basement membranes, which is required for metastasis and organoid growth.
Ultraviolet-radiation-induced inflammation promotes angiotropism and metastasis in melanoma
Bald T., Quast T., Landsberg J., Rogava M., Glodde n., Lopez-Ramos D., Kohlmeyer J., Riesenberg S., van den Boorn-Konijnenberg D., Hömig-Hölzel C., Reuten R., Schadow B., Weighardt H., Wenzel D., Helfrich I., Schadendorf D., Bloch W., Bianchi M.E., Lugassy C., Barnhill R.L., Koch M., Fleischmann B.K., Förster I., Kastenmüller W., Kolanus W., Hölzel M., Gaffal E., Tüting T. Nature Letter. 2014
The authors report that repetitive UV exposure of primary cutaneous melanomas in a genetically engineered mouse model promotes metastatic progression. UV irradiation enhanced the expansion of tumor cells along abluminal blood vessel surfaces and increased the number of lung metastases, depended on the recruitment and activation of neutrophils. In a static cell adhesion assays, cells were allowed to adhere to various matrices: fibronectin-1, collagen type I, collagen type IV, laminin-111 (Sigma), laminin-411 or laminin-511. An inflammatory environment promotes the ability of mouse and human melanoma cells to migrate towards endothelial cells and use selective motility cues on their surfaces.
Monoclonal antibodies to human laminin α4 chain globular domain inhibit tumor cell adhesion and migration on laminins 411 and 421, and binding of α6β1 integrin and MCAM to α4-laminins
Ishikawa T., Wondimu Z., Oikawa Y., Ingerpuu S., Virtanen I., Patarroyo M.Matrix Biology, 2014
α4-Laminins, such as laminins -411 and -421, are mesenchymal laminins expressed by vascular and lymphatic endothelial cells, leukocytes and other normal cell types. These laminins are recognized by α6β1 and α6β4 integrins and MCAM (CD146) and promote adhesion and migration of the cells. α4-Laminins are also expressed and secreted by some tumor cells and strongly promote tumor cell migration. Moreover, the abluminal side of blood and/or lymphatic vessels and the nerve perineurium, common tracks of tumor cell dissemination, express α4-laminins, and these laminin isoforms, when expressed in the stroma, may contribute to tumor invasion. In the present study, we examined ten mAbs to human laminin α4 chain for their reactivity with the isolated laminin α4 globular domain, their ability to inhibit tumor cell adhesion and migration on laminin-411 and -421, and their effect on the binding of α6β1 integrin and MCAM to both α4-laminins. The results indicate that mAbs to the laminin α4 globular domain are able to inhibit tumor cell adhesion and migration on laminin-411 and -421 and that α6β1 integrin and MCAM bind α4-laminins at very close sites on the globular domain. These reagents contribute to a better understanding of the biology of α4-laminins and may have a therapeutic potential in malignant and inflammatory diseases.
Expression and function of laminins in the embryonic and mature vasculature
Rupert Hallmann, Nathalie Horn, Manuel Selg, Olaf Wendler, Friederike Pausch, Lydia M Sorokin. Physiol Rev, 2005
The endothelial cell basement membranes have been shown to be unique with respect to their laminin isoform composition. This review outlines the unique structural and functional features of vascular basement membranes, with focus on the endothelium and the laminin family of glycoproteins.
Laminin heparin-binding peptides bind to several growth factors and enhance diabetic wound healing
Ishihara J., Ishihara A., Fukunaga K., Sasaki K., White M.J.V., Briquez P.S., Hubbell J.A.Nature Communications, 2018
In this article, the authors show that multiple laminin isoforms promiscuously bind to growth factors with high affinity, through their heparin-binding domains located in the α chain laminin-type G (LG) domains. These domains also bind to syndecan cell-surface receptors, promoting attachment of fibroblasts and endothelial cells. The authors explore the application of these multifunctional laminin HBDs in wound healing in the type-2 diabetic mouse and demonstrate that covalent incorporation of laminin HBDs into fibrin matrices improve retention of GFs and significantly enhances the efficacy of vascular endothelial cell growth factor (VEGF-A165) and platelet-derived growth factor (PDGF-BB) in promoting wound healing in vivo, under conditions where the GFs alone in fibrin are inefficacious.
Compositional Differences between Infant and Adult Human Corneal Basement Membranes
Kabosova A., Azar D.T., Bannikov G.A., Campbell K.P, Durbeej M., Ghohestani R.F., Jones J.C.R, Kenney M.C, Koch M., Ninomiya Y., Patton B.L., Paulsson M., Sado Y., Sage E.H., Sasaki T., Sorokin L.M., Steiner-Champliaud M-F, Sun T-T, SundarRaj N., Timpl R., Virtanen I., Ljubimov A.V. Invest Ophthalmol Vis Sci. 2007
The purpose of the study was to identify changes in the human corneal epithelial basement membrane (EBM) and Descemet's membrane (DM) during postnatal corneal development. Type IV collagen composition of infant corneal central EBM over Bowman's layer changed from α1-α2 to α3-α4 chains after 3 years of life; in the adult, α1-α2 chains were retained only in the limbal BM. Laminin α2 and β2 chains were present in the adult limbal BM where epithelial stem cells are located. By 3 years of age, β2 chain appeared in the limbal BM. In all corneas, limbal BM contained laminin γ3 chain. The stromal face of the infant but not the adult DM was positive for tenascin-C, fibrillin-1, SPARC, and laminin-332. Type VIII collagen shifted from the endothelial face of infant DM to its stromal face in the adult.
Corneal integrins and their functions
Stepp M.A.Experimental Eye Research, 2005
There is a minimum of 12 different integrin heterodimers reported to be expressed by the major resident cells of the cornea: the corneal and limbal epithelial cells, keratocytes/fibroblasts, and corneal endothelial cells. These different integrin heterodimers play important and varied roles in maintaining the cornea and organizing how its cells interact with their surrounding extracellular matrix to maintain corneal clarity. In this review, an overview of the discovery and functions of integrins is provided along with a description of the current state of our knowledge of this large family of important proteins.