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Query: UMLS:C1519670 (tumor angiogenesis)
 6,052 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumor growth is dependent on angiogenesis, which is thought to be mediated through growth factors, such as transforming growth factor-alpha (TGF-alpha) and -beta (TGF-beta), epidermal growth factor (EGF), and basic fibroblast growth factor (bFGF), produced by tumor cells. We have developed a model system for tumor angiogenesis in vitro: tube formation of human omentum microvascular endothelial (HOME) cells in type I collagen gels when these cells are co-cultured with tumor cells. Exogenously added TGF-alpha induced tube formation of HOME cells in collagen gel. In contrast, TGF-beta inhibited the TGF-alpha-induced tube formation of endothelial cells. We investigated whether tube formation could be induced in HOME cells in collagen gel when the HOME cells were co-cultured with three esophageal cancer cell lines, TE1, TE2, and TE5. TE1 and TE2 cells expressed both TGF-alpha and TGF-beta mRNA, but the level of TGF-alpha mRNA in TE2 was found to be much lower than in TE1 cells. TE5 did not express either TGF-alpha or TGF-beta. The tube formation of HOME cell was induced when they were co-cultured with TE1 cells, while both TE2 and TE5 cell lines induced tube formation at much lower rates than TE1. TE1-induced tube formation of HOME cells was specifically blocked by co-administration of anti-TGF-alpha-antibody, but not by anti-bFGF-antibody. The present study suggests that, in our model system, esophageal tumor angiogenesis is partly controlled by TGF-alpha, possibly through a paracrine pathway.
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PMID:A model system for tumor angiogenesis: involvement of transforming growth factor-alpha in tube formation of human microvascular endothelial cells induced by esophageal cancer cells. 138 Aug 4

Endothelial cell migration is a key feature of angiogenesis. Epidermal Growth Factor (EGF) or Tumor Angiogenesis Factor (TAF) induce cell migration and angiogenesis. When the matrix components, collagen or fibronectin, were used as a substratum in the phagokinesis assays, EGF- or TAF-induced cell migration was inhibited. It has been proposed that TAF activates cellular protease causing the matrix degradation that is evident during neovascularization in vitro. If such degradation leads to cell migration and angiogenesis, then other agents that interfere with the synthesis or assembly of matrix components should stimulate cell migration and angiogenesis. The proline analogues cis hydroxyproline, azetidine and dehydroproline are known modulators of cellular collagen synthesis. At optimal concentration (10(-5)M) these analogues caused 3-fold increases in endothelial cell migration rates in vivo as tested by a subcutaneous implant assay. We conclude from these studies that: (i) matrix components control cellular migration rates; high concentration of collagen or fibronectin inhibit angiogenically active inducers of endothelial cell migration. (ii) Intracellular modulation of synthesis of collagens leads to angiogenesis by stimulating cell migration. These findings relate to tumor angiogenesis and that TAF might trigger angiogenesis either by activation of latent proteases or by some modification of matrix assembly during synthesis that affects cell adhesion and migration.
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PMID:Matrix control of tumor angiogenesis. 246 16

We examined the effect of medroxyprogesterone acetate (MPA) on secondary spreading of endometrial cancer. There was no significant difference in the adhering capacity of dispersed Ishikawa cells (derived from well-differentiated endometrial cancer) to a cell basement membrane matrix, fibronectin or laminin between cells treated with MPA, with cortisol, and without treatment. The adhering capacity of cells treated with cortisol to collagen type IV was higher than that without treatment. However, the adhering capacity was little affected by treatment with MPA. These results indicate that although cortisol may induce the initial process of metastasis by inducing the attachment of tumor cells to the basement membrane of vascular endothelium, MPA has no influence on the attachment, although it has a glucocorticoid action similar to that of cortisol. There was no significant difference in tumor angiogenesis factor (TAF) or fibroblast growth factor (FGF) activity of the tumor extract from Ishikawa cell colonies between cortisol-treated and control group. TAF or FGF activity of the MPA-treated group was lower than that of the control group. MPA may reduce the neovascularization in the terminal process of metastasis via the reduction of TAF and FGF produced by tumor cells, in spite of its glucocorticoid action.
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PMID:Effect of medroxyprogesterone acetate on secondary spreading of endometrial cancer. 252 39

Epidermal growth factor (EGF) or transforming growth factor-alpha (TGF-alpha) stimulated cell migration, chemotaxis, and the expression of tissue-type plasminogen activator (t-PA) in human omental microvascular endothelial (HOME) cells. Hepatocyte growth factor (HGF) stimulated cell proliferation, but had a negligible stimulatory effect on cell migration, the expression of t-PA and tube-like formation into collagen gel in HOME cells. Basic fibroblast growth factor stimulated cell proliferation, cell migration, tubulogenesis and the expression of urokinase-type plasminogen activator (u-PA) in bovine aortic endothelial (BAE) cells. HOME and BAE cells had both high- and low-affinity receptors for HGF. In BAE cells, u-PA activity and tube-like structures in collagen gel were induced in the presence of HGF alone. In contrast, in HOME cells, t-PA activity and tube-like structures were induced in the presence of TGF-alpha alone, but not in the presence of HGF alone. However, we observed a marked induction of tube formation by HOME cells when both t-PA and HGF were added simultaneously. In the model system for tumor angiogenesis, when HOME cells were co-cultured with a renal cancer cell line, KPK13, tube-like structures were induced in the presence of HGF:KPK13 cells expressed large amounts of t-PA mRNA. Our present study suggested that HGF in concert with active t-PA could be angiogenic in HOME cells.
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PMID:Cooperative roles of hepatocyte growth factor and plasminogen activator in tubular morphogenesis by human microvascular endothelial cells. 750 7

We have established an in vitro angiogenesis model using human omental microvascular endothelial (HOME) cells, in which epidermal growth factor (EGF) or transforming growth factor-alpha (TGF-alpha) stimulated cell migration and tube formation. In this study, we examined whether alpha-guaiaconic acid (GR-12) and its synthetic 20 derivatives showed inhibition of cell migration and tubular formation of HOME cells. We found that GR-12 inhibits arachidonic acid metabolism, while GR-12 and one derivative, GS-01, inhibit tubular formation of endothelial cells in our model system. Confluent monolayers of HOME cells were damaged with a razor blade and incubated with or without TGF-alpha; HOME cell migration was stimulated about 1.5-fold over control values in the presence of TGF-alpha. Treatment of HOME cells with GR-12 or GS-01 inhibited both spontaneous and TGF-alpha-stimulated migration. GR-12 or GS-01 inhibited TGF-alpha-induced HOME-cell tube formation in type-1 collagen gels. We examined whether these compounds could modulate tubular formation of HOME cells induced by human cancer cells. Enhanced tube formation of HOME cells by co-cultured esophageal cancer cells was almost completely inhibited by co-administration of GR-12 or GS-01. Both compounds also inhibited formation of tubular networks of HOME cells on Matrigels. We also examined anti-angiogenic activity of these compounds in an in vivo model system of tumor angiogenesis in mice. In this system, GS-01 inhibited development of capillary networks at a rate comparable to that of a well-known anti-angiogenic compound, fumagillin, but GR-12 did not. The inhibitor of arachidonic acid metabolism is thus expected to modulate tumor angiogenesis.
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PMID:Anti-angiogenic activity of arachidonic acid metabolism inhibitors in angiogenesis model systems involving human microvascular endothelial cells and neovascularization in mice. 769 64

TSP-1 is a matrix-bound adhesive glycoprotein, which plays a role in tumor cell proliferation and tumor angiogenesis. The purpose of this study was to investigate the effect of TSP-1 on breast tumor cell invasion. Tumor cell invasion assays were performed using a modified Boyden chamber apparatus with collagen-coated membranes. Four breast cell lines were studied in serum-free media: the malignant MDA-MB-231, SKBR-3, and MCF-7 cell lines, and the benign MCF-10A cell line. Invasion was measured as the summation of the number of cells in five representative high power fields (400x) traversing the collagen barrier after a 3-hr incubation period. The effect of an anti-TSP-1 antibody (100 microgram/ml) was also evaluated in the malignant cell lines. Statistical analysis was performed by ANOVA and Student's unpaired t test. TSP-1 promoted a dose-dependent increase in invasion as compared to buffer controls in all three malignant cell lines. TSP-1 (100 nM) promoted a greater than five-fold increase over controls in tumor cell invasion for MDA-MB-231, SKBR-3, and MCF-7 cell lines (P < 0.005). TSP-1 had no effect on the invasiveness of the benign cell type MCF-10A. Anti-TSP-1 antibody inhibited TSP-1 promoted invasion in the MDA-MB-231, SKBR-3, and MCF-7 cell lines by 45, 48, and 39%, respectively (P = 0.003, 0.044, 0.047). TSP-1 promotes tumor cell invasion of collagen by breast cancer cells. Therapy designed to inhibit TSP-1 may prevent invasion and metastasis in breast cancer.
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PMID:Thrombospondin-1 (TSP-1) promotes the invasive properties of human breast cancer. 866 Nov 69

Choroidal and ciliary body melanomas disseminate exclusively by a hematogenous route because there are no lymphatics inside the eye. Although angiogenesis is an absolute precondition for metastasis in this tumor system, not all morphologic expressions of tumor angiogenesis are associated with metastasis from choroidal and ciliary body melanomas. Specifically, the remodeling of the microcirculation to form vascular networks is very strongly associated with metastasis. Type VI collagen is upregulated in tissue remodeling and the generation of tissue patterns and is either not present in the normal choroid or present at very low levels. This study was designed to investigate the possible expression of type VI collagen in the stroma of choroidal and ciliary body melanomas. Type VI collagen was detected in tissue sections from five primary choroidal melanomas and three melanomas involving the choroid and ciliary body in the subendothelial compartment of the microcirculation and in avascular areas by immunohistochemistry. Melanoma cell lines were established from each of these tumors. Cultured melanoma cells invaded into type I collagen gels and expressed type VI collagen by immunohistochemistry. Using specific primers for human type VI collagen, the expected band size (413 base pairs) was isolated from one of the cell lines by reverse transcriptase PCR. The presence of type VI collagen in the melanoma tumor stroma reflects active remodeling of the uveal extracellular matrix microenvironment by the melanoma cells themselves. Before the formation of the microvasculature, the expression of type VI collagen and of the other matrix components, such as hyaluronan, to which it binds, may erect a scaffold permitting the formation of higher order stromal patterns such as vascular networks. These stromal patterns, which are markers of tumor progression, may be detectable clinically by a specialized form of ultrasonography that detects backscatterers of the same dimension as tissue compartments encircled by vascular loops in networks.
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PMID:Expression of type VI collagen in uveal melanoma: its role in pattern formation and tumor progression. 868 40

Scatter factor (SF) is an angiogenic growth factor that stimulates motility and invasion of carcinoma cells. SF is present in the extracellular matrix (ECM) of breast cancers, where it might act to promote tumor cell invasion and angiogenesis. To investigate how SF is incorporated into the ECM, we studied the binding of SF to various ECM components using a solid-phase binding assay based on the SF enzyme-linked immunosorbent assay. We found that SF binds to a variety of ECM molecules, with different binding capacities. The highest SF binding capacities were observed for thrombospondin-1 (TSP-1), fibronectin (Fn), and heparan sulfate proteoglycan, although SF did not bind to albumin. Mature two-chain SF and precursor single-chain SF bound approximately equally well to TSP-1 and Fn. Moreover, two SF alpha-chain peptides (NK1 and NK2) both bound to TSP-1 and Fn, suggesting that the whole SF molecule is not required for binding. Based on binding competition assays, TSP-1 exhibited higher affinity for SF than did nine other ECM molecules, including Fn and heparan sulfate proteoglycan. Although heparin in solution potently inhibited the binding of SF to TSP-1-coated surfaces, even very high concentrations of heparin could not elute SF already bound to TSP-1. SF binding was modulated by binding interactions among ECM molecules (TSP-1-Fn, TSP-1-collagen I, and Fn-collagen I), suggesting that the matrix capacity to bind SF depends upon its exact composition. SF bound in a dose-dependent fashion to ECMs secreted by three human breast carcinoma cell lines. Binding of SF to matrices from all three cell lines was significantly inhibited by preincubation of the matrices with antibodies against TSP-1, whereas antibodies against several other ECM components were less effective or ineffective in inhibiting SF binding. In addition, TSP-1 markedly inhibited chemotaxis of microvascular endothelial cells toward SF and SF-induced angiogenesis in the rat cornea neovascularization assay. Our findings suggest that 1) SF interacts with a variety of ECM components, 2) high affinity SF-TSP-1 interactions may mediate the binding of SF to the breast cancer matrix, and 3) the SF-TSP-1 interaction may contribute to modulation of angiogenesis. Possible implications of these findings for tumor angiogenesis are discussed.
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PMID:Scatter factor binds to thrombospondin and other extracellular matrix components. 878 Mar 85

Intussusceptive microvascular growth (IMG) is a new mechanism of capillary growth: The vascular network expands by insertion of newly formed columns of interstitial tissue (interstitial tissue structures) into the vascular lumen called tissue pillars or posts (diameter: 0.5-2.5 microm). IMG has so far been described during organ development and growth and in tumor angiogenesis. Different modes of its implementation could be demonstrated in the rat lung and the chicken chorioallantoic membrane (CAM). In the present investigation a further mechanism of IMG is reported in the chicken CAM: tissue pillars form by splitting of larger interstitial tissue structures and intercapillary walls located between neighboring capillary segments which will consecutively fuse. Splitting is dependent on the existence of a pillar's core composed of a bundle of collagen fibrils ensheathed by extensions of endothelial-like cells inside these structures. Pillar cores thus represent the smallest unit of interstitial tissue around which the vascular lumen might expand. This mode of IMG is obviously connected to physiological remodeling of the capillary network and appears to be dominant during later stages of CAM development.
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PMID:Implementation of intussusceptive microvascular growth in the chicken chorioallantoic membrane (CAM). 905 74

Endothelial cells involved in tumor angiogenesis, wound healing, and inflammation are predominantly of microvascular origin and are functionally distinct from large vessel-derived endothelial cells which have been largely used for in vitro vascular research. To overcome the problems commonly involved in the culture of microvascular endothelial cells, including unreliable isolation techniques and low cell yields, we developed a simplified protocol for the selective cultivation of human dermal microvascular endothelial cells (HDMEC) obtained from neonatal foreskins, based on the transient, endothelial cell-specific induction of E-selection by tumor necrosis factor-alpha (TNF-alpha). Subconfluent primary cultures, consisting of a mixture of endothelial cells, fibroblasts, and keratinocytes, were treated with TNF-alpha for 6 h, and HDMEC were isolated by their selective binding to magnetic beads coupled with anti-E-selection monoclonal antibody. After two immunomagnetic purification steps, a homogenous population of HDMEC was obtained which showed typical cobblestone morphology, expressed CD31 and von Willebrand factor, proliferated in response to vascular endothelial growth factor, upregulated the expression of intercellular adhesion molecule-1 and vascular adhesion molecule-1 in response to TNF-alpha, and formed capillary-like tubes in a three-dimensional collagen type I matrix. This simple technique may facilitate a more widespread use of microvascular endothelial cell cultures obtained from different human or animal organs for functional in vitro studies.
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PMID:A simple immunomagnetic protocol for the selective isolation and long-term culture of human dermal microvascular endothelial cells. 957 Sep 15


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