Modulation of Angiogenesis in Vitro by Laminin-Entactin Complex

Nicosia, Roberto F.; Bonanno, Elena; Smith, M. R.; Yurchenco, Peter D.

doi:10.1006/dbio.1994.1191

Cited by 67 publications

(36 citation statements)

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“…40 -44 Moreover, laminin-1 has been shown to play an important modulatory role in angiogenesis by stabilization of microvessels. 45 Our histologic and immunohistochemic study of the laminin-␣1-expressing tumors developed in nude mice shows that despite the absence of major modifications in the tumor differentiation or invasion potential, changes in deposition of some basement membrane components such as laminin-10 (␣5␤1␣1) and in the ␤4 integrin deposition were obvious. These data are complementary to those observed by implanting the formerly described laminin ␣1 antisense targeted Caco2 cells.…”

Section: Discussionmentioning

confidence: 85%

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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Section: Discussionmentioning

confidence: 85%

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

et al. 2001

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“…We previously reported that aorta-derived microvessels survived longer if cultured in collagen gels supplemented with high doses of basement membrane molecules (Nicosia et al, 1994a). We also found that disruption of endothelial cell-ECM interactions with RGD-containing peptides caused disintegration of neovessels (Nicosia and Bonanno, 1991;Nicosia et al, 1993a).…”

Section: Matrix Metalloproteinases and Vascularmentioning

confidence: 94%

Regulation of Vascular Growth and Regression by Matrix Metalloproteinases in the Rat Aorta Model of Angiogenesis

Zhu

Guo

Villaschi

et al. 2000

Laboratory Investigation

117

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SUMMARY:Matrix metalloproteinases (MMPs) have been implicated in the formation of microvessels during angiogenesis, but their role in vascular regression is poorly understood. The rat aorta model of angiogenesis was used to study the function of MMPs at different stages of the angiogenic process. Gelatin zymography and Western analysis demonstrated production of MMP-2 and MMP-9 by aortic outgrowths in serum-free collagen gel culture. MMP-2 was found in both culture medium and collagen gel, whereas MMP-9 was predominantly associated with the gel. MMP expression increased gradually during the angiogenic growth phase and stayed high when vessels regressed and collagen lysed around the aortic rings. The MMP inhibitors, batimastat and marimastat, blocked formation of microvessels when added to the culture medium at the beginning of the experiment. They, however, stabilized the microvessels and prevented vascular regression after the angiogenic growth phase. This effect was observed also under conditions of angiogenic stimulation by basic fibroblast growth factor. MMP inhibitormediated stabilization of microvessels was associated with inhibition of collagen lysis and accumulation of collagen fibrils in the subendothelial space. This study demonstrates that MMPs promote microvessel formation during the early stages of angiogenesis, but also contribute to the reabsorption of the neovasculature in the later stages of this process. The time-dependent divergent effects of MMPs on microvessel growth and survival may influence the in vivo activity of MMP inhibitors used to treat angiogenesis-dependent disorders. (Lab Invest 2000, 80:545-555).

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“…26 Laminin and its binding protein entactin exhibit similar dual roles in angiogenesis. 78,79 Here, however, some insight is gained by the concentration dependence of laminin-entactin complexes on vessel formation. 79 When laminin-entactin is offered to the cells at low concentrations, angiogenesis is facilitated, whereas application of lamininentactin at high concentrations inhibits angiogenesis.…”

Section: Angiogenesismentioning

confidence: 99%