Basement membrane complexes with biological activity

Kleinman, Hynda K.; McGarvey, Mary L.; Hassell, John R.; Star, Vicki L.; Cannon, Frances B.; Laurie, Gordon W.; Martin, George R.

doi:10.1021/bi00350a005

Cited by 1,361 publications

(741 citation statements)

References 48 publications

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“…Previous studies suggest that strong interactions between laminin and invasive tumor cells enhance the metastatic propensity of the tumor cells by allowing them to cross the basement membrane more readily. In addition, the interactions of laminin with ECM components and the lamininlaminin interactions play important roles in matrix organization (21,22,34).…”

Section: Discussionmentioning

confidence: 99%

Structures and Dynamic Motion of Laminin-1 As Observed by Atomic Force Microscopy

1998

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Laminins are a family of multifunctional extracellular matrix glycoproteins that play important roles in the development and maintenance of tissue organization via their interactions with cells and other extracellular matrix proteins. To understand the structural basis of laminins' functions, we examined the motion of laminin-1 (Ln-1) in physiological buffers using atomic force microscopy. While many Ln-1 molecules assumed the expected cruciform structure, unexpected dynamic movements of the Ln-1 arms were observed in aqueous environments. These dynamic movements of the Ln-1 arms may contribute to the diversity of laminin functions.

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Section: Discussionmentioning

confidence: 99%

Structures and Dynamic Motion of Laminin-1 As Observed by Atomic Force Microscopy

1998

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“…allows the assessment of tumor cell migration through Matrigel, a reconstituted basement membrane also known as Engelbreth-Holm-Swarm matrix (26). This assay mimics the early steps of tumor invasion in vivo, namely the degradation of, and migration through, basement membranes (27).…”

Section: Stromelysin-1 Antisense Treatment Blocks Matrigel Invasionmentioning

confidence: 99%

Misregulation of Stromelysin-1 Expression in Mouse Mammary Tumor Cells Accompanies Acquisition of Stromelysin-1-dependent Invasive Properties

Lochter

Srebrow

Sympson

et al. 1997

Journal of Biological Chemistry

135

128

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Stromelysin-1 is a member of the metalloproteinase family of extracellular matrix-degrading enzymes that regulates tissue remodeling. We previously established a transgenic mouse model in which rat stromelysin-1 targeted to the mammary gland augmented expression of endogenous stromelysin-1, disrupted functional differentiation, and induced mammary tumors. A cell line generated from an adenocarcinoma in one of these animals and a previously described mammary tumor cell line generated in culture readily invaded both a reconstituted basement membrane and type I collagen gels, whereas a nonmalignant, functionally normal epithelial cell line did not. The matrix metalloproteinases (MMPs) 1 are a family of extracellular matrix (ECM)-degrading enzymes that have been implicated in a variety of normal developmental and pathological processes, including tumorigenesis (1, 2). The MMP family comprises at least 15 members with different, albeit overlapping, substrate specificities. During activation of latent MMPs, their propeptides are cleaved and they are converted to a lower molecular weight form by other enzymes, including serine proteinases, and by autocatalytic cleavage.Among the MMPs, stromelysin-1 (SL1) possesses the broadest substrate specificity (1). Despite increasing knowledge about its enzymatic properties and the regulation of its expression, little is known about its function. We have generated transgenic animals that express an autoactivating mutant of rat SL1 targeted to the epithelial compartment of the mammary gland (3). Phenotypically, SL1 transgenic mice display increased branching morphogenesis and lactogenic differentiation at prepubertal stages and premature involution during late pregnancy (3, 4). Branching morphogenesis requires the invasion of epithelial cells into the adipose tissue, a process reminiscent of invasion of stromal compartments by tumor cells. Strikingly, a large number of SL1 transgenic animals also develop mammary tumors of various histotypes, including invasive adenocarcinomas (5). 2 Because tumor development is a late response of SL1 transgenic mice to overexpression of the transgene, it remains unclear whether SL1 plays a direct role in tumor growth and/or invasion or whether the observed tumors are a consequence of other molecular alterations in the microenvironment of the mammary gland before the onset of tumor growth. 3 Studies performed with synthetic inhibitors of MMP activity and tissue inhibitors of metalloproteinases (TIMPs) have shown that suppression of MMP activity also suppresses tumor growth and metastasis (6, 7). In many cases, the level of SL1 expression in tumors of the mammary gland and other tissues is positively correlated with the degree of malignancy (8, 9). However, the only direct evidence for the nature of the MMPs involved was provided by the demonstration that function-blocking antibodies against gelatinase A and antisense inhibition of matrilysin expression decreased the invasiveness of tumor cells in a reconstituted basement membrane assay (10, 11). The...

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“…There was also no difference in the migration of MEF-1 and MEF-2 cells in wells coated with Matrigel. Matrigel is a complex mixture of basement membrane proteins; however, the major components are laminin and type IV collagen, with minimal vitronectin (50). In wells that were precoated with purified fibronectin, MEF-2 cells migrated at a significantly increased velocity compared with MEF-1 cells (p Ͻ 0.01); however, the magnitude of the effect was only 50% of that observed with vitronectin.…”

Section: Migration Of Mef-1 and Mef-2 Cells In Serum-supplemented Medmentioning

confidence: 99%

Embryonic Fibroblasts That Are Genetically Deficient in Low Density Lipoprotein Receptor-related Protein Demonstrate Increased Activity of the Urokinase Receptor System and Accelerated Migration on Vitronectin

Weaver

Hussaini

Mazar

et al. 1997

Journal of Biological Chemistry

100

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Low density lipoprotein receptor-related protein (LRP) mediates the endocytosis of diverse ligands, including urokinase plasminogen activator (uPA) and its receptor, uPAR, which have been implicated in cellular migration. The purpose of this study was to determine whether LRP affects cellular migration. Murine embryonic fibroblasts (MEF) that are LRP-deficient due to targeted gene disruption and exotoxin selection (MEF-2), heterozygous fibroblasts (PEA-10), and wild-type fibroblasts (MEF-1) were compared. When cultures were denuded of cells in a 1-mm-wide strip, all three cell types migrated into the denuded area. The MEF-2 cells migrated nearly twice as rapidly as the MEF-1 cells or PEA-10 cells. The difference in migration velocity was duplicated in culture wells that were precoated with serum or vitronectin and partially duplicated in wells coated with fibronectin but not in wells coated with type I collagen or Matrigel. uPA was detected in MEF-2 conditioned medium (CM) at a concentration of 0.30 ؎ 0.02 nM, which was 13-fold higher than the level detected in MEF-1 CM or PEA-10 CM, suggesting one potential mechanism for the enhanced migration of MEF-2 cells. uPAR was also increased on MEF-2 cells by 4 -5-fold, as determined by PI-PLC release, and by 2.5-fold, as determined by a uPA/uPAR activity assay. Mannosamine treatment, which down-regulates cell-surface uPAR, decreased MEF-2 migration by 40% without significantly affecting MEF-1 migration. MEF-2 CM, which is uPArich, increased the rate of MEF-1 migration, and MEF-1 CM did not. These studies demonstrate alterations in cellular migration and in the activity of the uPA/uPAR system which accompany complete deficiency of LRP expression in fibroblasts. We propose that uPA and uPAR form an autocrine loop for promoting fibroblast migration and that LRP counteracts the activity of this system.

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Basement membrane complexes with biological activity

Cited by 1,361 publications

References 48 publications

Structures and Dynamic Motion of Laminin-1 As Observed by Atomic Force Microscopy

Structures and Dynamic Motion of Laminin-1 As Observed by Atomic Force Microscopy

Misregulation of Stromelysin-1 Expression in Mouse Mammary Tumor Cells Accompanies Acquisition of Stromelysin-1-dependent Invasive Properties

Embryonic Fibroblasts That Are Genetically Deficient in Low Density Lipoprotein Receptor-related Protein Demonstrate Increased Activity of the Urokinase Receptor System and Accelerated Migration on Vitronectin

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