Proteolytic modification of laminins: Functional consequences

Ghosh, Supurna; Stack, M. Sharon

doi:10.1002/1097-0029(20001101)51:3<238::aid-jemt4>3.0.co;2-3

Cited by 45 publications

(42 citation statements)

References 88 publications

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“…Laminins are important for cell adhesion, migration, growth, and differentiation (17)(18)(19). They are heterotrimeric glycopro- teins that constitute a major component of basement membranes.…”

Section: Discussionmentioning

confidence: 99%

Laminin Modulates Morphogenic Properties of the Collagen XVIII Endostatin Domain

Javaherian¹,

Park²,

Pickl³

et al. 2002

Journal of Biological Chemistry

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We have shown previously that the oligomeric endostatin domain of collagen XVIII (NC1) functioned as a motility-inducing factor regulating the extracellular matrix-dependent morphogenesis of endothelial cells. This motogenic activity gave rise to structures resembling filipodia and lamellipodia and was dependent on Rac, Cdc42, and mitogen-activated protein kinase. Here, we demonstrate that these properties of endostatin are primarily mediated by laminin in the basement membrane and heparan sulfates on the cell surface. The sites of interaction between laminin and oligomeric endostain include the N-terminal regions of all three laminin chains (amino acids 204 -1243 of the ␣ chain, 932-1161 of the ␤ chain, and 150 -965 of the ␥ chain). A monoclonal antibody that blocks the interactions between endostatin and laminin was utilized to inhibit the motogenic activity of endostatin. In parallel, we have engineered selective point mutations and produced recombinant forms that lack binding to heparan sulfates on the cell surface. Our data are consistent with a model of endostatin with two binding sites: one mainly to laminin in the basement membrane and the other to heparan sulfates on the cell surface. The two binding domains on endostatin appear to be separate with the possibility of some overlap between the two sites.

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Section: Discussionmentioning

confidence: 99%

Laminin Modulates Morphogenic Properties of the Collagen XVIII Endostatin Domain

Javaherian¹,

Park²,

Pickl³

et al. 2002

Journal of Biological Chemistry

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“…Also, type IV collagenase activity in melanoma and fibrosarcoma cells is upregulated by intact laminin [42]. Expression of plasminogen activators, which are involved in activating matrix-degrading proteinases, is regulated by laminin-1 [43]. Laminin-5 normally promotes static adhesion and hemidesmosome formation between cells; however, MMP-1, -2, and MT1-MMP cleave laminin-5, and a resulting fragment stimulates cell migration and invasion [36,44].…”

Section: Invasionmentioning

confidence: 99%

“…For example, a 25 kDa thrombospondin fragment has been shown to promote angiogenesis, whereas several other ECM fragments inhibit it, including endostatin (derived from collagen XVIII), angiostatin (from plasminogen), the NCI domains of collagen IV, several thrombospondin peptides and endorepellin (derived from the C-terminus of perlecan) [65][66][67][68][69][70]. Fragments and synthetic peptides derived from laminin have also been found to regulate angiogenesis [43]. Laminin is present in the endothelial basement membrane, and more than 20 peptides from laminin-1 that can promote angiogenesis in vivo have been identified [22,23].…”

Section: Angiogenesismentioning

confidence: 99%

The basement membrane matrix in malignancy

Engbring

Kleinman

2003

The Journal of Pathology

216

167

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Cancer is the second most common cause of death among Americans, although for several age groups it ranks first. Most of these deaths are not due to the primary tumour but rather to tumour cell metastases to distant organs. There are many steps that lead to metastasis, all of which are being studied with the goal of preventing these fatalities. Normally, cells attach to the extracellular matrix to maintain tissue integrity. During cancer progression, cells become more motile and acquire invasive qualities. Tumour cells move along blood and lymph vessels or invade into them to travel to distant sites. Then, the tumour cells must attach to the vessel wall, extravasate from the vessel, invade the new tissue, proliferate, and form a secondary tumour. Angiogenesis, the formation of new blood vessels, is critical to survival of these cells at the new site and is also important for primary tumour growth and spread. Tumour cell metastasis is a complex cascade of sequential steps, each of which is not yet fully understood. Progress has been made in identifying several key activators, one of which is the extracellular matrix. A major tumour promoter is the glycoprotein laminin, which is predominantly found in the extracellular matrix produced by endothelial and epithelial cells. This review will follow the metastatic process with particular attention to the effect of laminin on tumour cells.

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“…300 and approx. 100 kD were visualized; this might correspond to degradation products of the ␣1 chains known to be susceptible to proteolysis 29 or to the presence of unidentified protein(s). Substantial ␣1-chain degradation products were already observed in the recombinant mammalian strategy used to analyze laminin assembly and secretion.…”

Section: General Characteristics Of Ht29 Cells Induced To Express Thementioning

confidence: 99%

Overexpression of laminin ?1 chain in colonic cancer cells induces an increase in tumor growth

et al. 2001

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Laminins represent a growing family of glycoproteins constituting the basement membrane. They are known to direct many biological processes. With respect to carcinogenesis, laminins play an important role in cell adhesion, mitogenesis, differentiation and even metastasis. To further study the biological significance of laminin-1 (composed of ␣1, ␤1 and ␥1 chains) in intestinal cell differentiation or tumorigenesis, an ␣1-laminin expression vector was introduced into the HT29 colonic cancer cells, in which laminin ␣1 chain is not expressed. Upon transfection of the ␣1 chain, the ␣1␤1␥1 trimer was found secreted in the media along with free Key words: laminins; basement membrane; colonic cancer cells; tumor growth; differentiationIt is well established that in multicellular organisms, extracellular matrix molecules control various physiologic activities such as cell growth, migration, apoptosis and differentiation. The extracellular network includes the interstitial matrix and basement membranes. The basement membranes that separate the connective tissue from epithelia, muscle fibers, blood vessels and nerves are formed by a complex set of collagens and of noncollagenous glycoproteins such as laminins, nidogen and of proteoglycans, which have a unique composition in each organ. Laminins are multifunctional molecules forming a family of proteins that display organ, site and developmental specificity. 1,2 The first characterized laminin isoform, laminin-1 (composed of ␣1, ␤1 and ␥1 chains), is a crosslike-shaped molecule assembled into a triplestranded coiled-coil structure designated as the long arm. 3 As for the other extracellular matrix molecules, laminin-1 is made up of specific structural domains that allow self-assembly, permit interaction with other basement membrane molecules and encode information for the cells via specific transmembrane receptors, mostly of the integrin family. 4 Recent studies performed on various organs during development show that laminin-1 has a rather limited expression. 5 Despite such restricted expression, crucial roles for laminin-1 in organ development and in cell differentiation have been demonstrated by cell-coating experiments, blocking antibody and antisense strategies. Several major functions have been assigned to the constitutive ␣1 chain of laminin-1, among which are the polarization of developing kidney tubules, 6,7 lung alveolar formation, 8 development of submandibular glands 9 and polarization and functional differentiation of mammary and intestinal cells. 10,11 Conversely, alterations in cell-matrix and cell-cell interactions have been shown in a number of pathologic situations, such as inflammatory processes, wound healing and malignant transformation. In colorectal cancer, perturbations in the production, deposition and degradation of matrix molecules, among which are laminins, have been observed. [12][13][14][15][16] The role of laminin-1 in tumor growth and metastasis has been evaluated in several cell systems. In particular, it was shown that coinjection of puri...

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Proteolytic modification of laminins: Functional consequences

Cited by 45 publications

References 88 publications

Laminin Modulates Morphogenic Properties of the Collagen XVIII Endostatin Domain

Laminin Modulates Morphogenic Properties of the Collagen XVIII Endostatin Domain

The basement membrane matrix in malignancy

Overexpression of laminin ?1 chain in colonic cancer cells induces an increase in tumor growth

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