Invasive Capacity (invasive + capacity)

Distribution by Scientific Domains


Selected Abstracts


Thioredoxin alters the matrix metalloproteinase/tissue inhibitors of metalloproteinase balance and stimulates human SK-N-SH neuroblastoma cell invasion

FEBS JOURNAL, Issue 2 2001
Antonietta R. Farina
Thioredoxin (Trx) inhibited tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 activity with an approximate IC50 of 0.3 µm, matrix metalloproteinase (MMP)-2 activity with an approximate IC50 of 2 µm but did not inhibit MMP-9 activity. This differential capacity of Trx to inhibit TIMP and MMP activity resulted in the promotion of MMP-2 and MMP-9 activity in the presence of molar TIMP excess. Inhibition of TIMP and MMP-2 activity by Trx was dependent upon thioredoxin reductase (TrxR), was abolished by Trx catalytic site mutation and did not result from TIMP or MMP-2 degradation. HepG2 hepatocellular carcinoma cells induced to secrete Trx inhibited TIMP activity in the presence of TrxR. SK-N-SH neuroblastoma cells secreted TrxR, which inhibited TIMP and MMP-2 activity in the presence of Trx. Trx stimulated SK-N-SH invasive capacity in vitro in the absence of exogenous TrxR. This study therefore identifies a novel extracellular role for the thioredoxin/thioredoxin reductase redox system in the differential inhibition of TIMP and MMP activity and provides a novel mechanism for altering the TIMP/MMP balance that is of potential relevance to tumor invasion. [source]


Elastin-derived peptides: Matrikines critical for glioblastoma cell aggressiveness in a 3-D system

GLIA, Issue 16 2009
Bérénice Coquerel
Abstract In the most common primary brain tumors, malignant glioma cells invade the extracellular matrix (ECM) and proliferate rapidly in the cerebral tissue, which is mainly composed of hyaluronan (HA) along with the elastin present in the basement membrane of blood vessels. To determine the role of ECM components in the invasive capacity of glioma cell lines, we developed a 3-D cell-culture system, based on a hydrogel in which HA can be coreticulated with kappa-elastin (HA-,E). Using this system, the invasiveness of cells from four glioma cell lines was dramatically increased by the presence of ,E and a related, specific peptide (VGVAPG)3. In addition, MMP-2 secretion increased and MMP-12 synthesis occurred. Extracellular injections of ,E or (VGVAPG)3 provoked a pronounced and dose-dependent increase in [Ca2+]i. ,E significantly enhanced the expression of the genes encoding elastin-receptor and tropoelastin. We propose the existence of a positive feedback loop in which degradation of elastin generates fragments that stimulate synthesis of tropoelastin followed by further degradation as well as migration and proliferation of the very cells responsible for degradation. All steps in this ECM-based loop could be blocked by the addition of either of the EBP antagonists, lactose, and V-14 peptide, suggesting that the loop itself should be considered as a new therapeutic target. © 2009 Wiley-Liss, Inc. [source]


The hemopexin domain of MMP-9 inhibits angiogenesis and retards the growth of intracranial glioblastoma xenograft in nude mice

INTERNATIONAL JOURNAL OF CANCER, Issue 2 2009
Ravesanker Ezhilarasan
Abstract Matrix Metalloproteinase-9 (MMP-9) consists of a prodomain, catalytic domain with 3 fibronectin-like type II modules and C-terminal hemopexin-like (PEX) domain. These domains play distinct roles in terms of proteolytic activity, substrate binding and interaction with inhibitors and receptors. To assess the potential of the MMP-9-PEX domain to interfere with tumor progression, we stably transfected human glioblastoma cells with an expression vector containing a cDNA sequence of the MMP-9-PEX. The selected clones exhibited decreased MMP-9 activity and reduced invasive capacity. We assessed how secretion of MMP-9-PEX by glioblastoma cells affects angiogenic capabilities of human microvascular endothelial cells (HMECs) in vitro. MMP-9-PEX conditioned medium treatment caused a reduction in migration of HMECs and inhibited capillary-like structure formation in association with suppression of vascular endothelial growth factor (VEGF) secretion and VEGF receptor-2 protein level. The suppression of HMECs survival by conditioned medium from MMP-9-PEX stable transfectants was associated with apoptosis induction characterized by an increase in cells with a sub-G0/G1 content, fragmentation of DNA, caspase-3, -8 and -9 activation and poly (ADP-ribose) polymerase (PARP) cleavage. A significant tumor growth inhibition was observed in intracranial implants of MMP-9-PEX stable transfectants in nude mice with attenuation of CD31 and MMP-9 protein expression. These results demonstrate that MMP-9-PEX inhibits angiogenic features of endothelial cells and retards intracranial glioblastoma growth. © 2008 Wiley-Liss, Inc. [source]


In vitro markers for virulence in Yersinia ruckeri

JOURNAL OF FISH DISEASES, Issue 3 2010
E Tobback
Abstract In this study, different traits that have been associated with bacterial virulence were studied in Yersinia ruckeri. Two isolates that had been shown to cause disease and mortality in experimentally infected rainbow trout were compared with five avirulent isolates. Both virulent isolates showed high adhesion to gill and intestinal mucus of rainbow trout, whereas the majority of non-virulent strains demonstrated significantly lower adhesion. A decrease in adherence capability following bacterial treatment with sodium metaperiodate and proteolytic enzymes suggested the involvement of carbohydrates and proteins. All strains were able to adhere to and invade chinook salmon embryo cell line (CHSE-214), fathead minnow epithelial cell line (FHM) and rainbow trout liver cell line (R1). One non-virulent strain was highly adhesive and invasive in the three cell lines, whereas the virulent strains showed moderate adhesive and invasive capacity. The internalization of several isolates was inhibited by colchicine and cytochalasin-D, suggesting that microtubules and microfilaments play a role. For all strains, intracellular survival assays showed a decrease of viable bacteria in the cells 6 h after inoculation, suggesting that Y. ruckeri is not able to multiply or survive inside cultured cells. Analysis of the susceptibility to the bactericidal effect of rainbow trout serum demonstrated that virulent Y. ruckeri strains were serum resistant, whereas non-virulent strains were generally serum sensitive. [source]


Blocking Wnt/LRP5 signaling by a soluble receptor modulates the epithelial to mesenchymal transition and suppresses met and metalloproteinases in osteosarcoma Saos-2 cells

JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 7 2007
Yi Guo
Abstract We previously reported the Wnt receptor low-density lipoprotein receptor-related protein 5 (LRP5) was frequently expressed in osteosarcoma (OS) tissue and correlated with metastasis and a lower disease-free survival. Subsequent in vitro analysis revealed that dominant-negative, soluble LRP5 (sLRP5) can reduce in vitro cellular invasion. In the current study, we examined the molecular mechanisms of blocking canonical Wnt signaling by sLRP5 in Saos-2 osteosarcoma cells. Transfection of sLRP5 caused a marked up-regulation of E-cadherin in this cell line. This increase in E-cadherin, seen primarily at the cell,cell contact borders, was associated with down-regulation of Slug and Twist, transcriptional repressors which mediate cancer invasion and metastasis. In contrast, N-cadherin, a mesenchymal marker, was reduced by sLRP5. In addition, blocking Wnt signaling by sLRP5 modulated other epithelial and mesenchymal markers (keratin 8 and 18, fibronectin), suggesting a reversal of epithelial,mesenchymal transition (EMT) seen during cancer progression. SLRP5 also reduced the expression of matrix metalloproteinase (MMP) 2 and 14, consistent with a decrease in invasive capacity. SLRP5 transfection decreased both Met expression and hepatocyte growth factor (HGF)-induced cell motility. Taken together, these results support a role for Wnt/LRP5 signaling in invasiveness of a subset of OS cells. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:964,971, 2007 [source]


Enhanced monocyte migration and pro-inflammatory cytokine production by Porphyromonas gingivalis infection

JOURNAL OF PERIODONTAL RESEARCH, Issue 2 2010
A. Pollreisz
Pollreisz A, Huang Y, Roth GA, Cheng B, Kebschull M, Papapanou PN, Schmidt AM, Lalla E. Enhanced monocyte migration and pro-inflammatory cytokine production by Porphyromonas gingivalis infection. J Periodont Res 2009; doi: 10.1111/j.1600-0765.2009.01225.x. © 2009 The Authors. Journal compilation © 2009 Blackwell Munksgaard Background and Objective:,Porphyromonas gingivalis, a major periodontal pathogen, has been reported to be involved in atherogenesis. In order to further understand this pathogen's link with systemic inflammation and vascular disease, we investigated its influence on murine monocytes and macrophages from three different sources. Material and Methods:, Concanavalin A-elicited peritoneal macrophages, peripheral blood monocyte-derived macrophages and WEHI 274.1 monocytes were infected with either P. gingivalis 381 or its non-invasive fimbriae-deficient mutant, DPG3. Results:, Infection with P. gingivalis 381 markedly induced monocyte migration and significantly enhanced production of the pro-inflammatory cytokines, tumor necrosis factor-, and interleukin-6. Consistent with a role for this pathogen's major fimbriae and/or its invasive capacity, infection with DPG3 had a minimal effect on both monocyte attraction and pro-inflammatory cytokine production. Conclusion:, Since monocyte recruitment and activation are important steps in the development of vascular inflammation and atherosclerosis, these results suggest that P. gingivalis infection may be involved in these processes. [source]


Establishment of a matrix-associated transepithelial resistance invasion assay to precisely measure the invasive potential of synovial fibroblasts

ARTHRITIS & RHEUMATISM, Issue 9 2009
Christina Wunrau
Objective Synovial fibroblasts (SFs) contribute to several aspects of the pathogenesis of rheumatoid arthritis (RA) and have been implicated most prominently in the progressive destruction of articular cartilage. Targeting the invasive phenotype of RASFs has therefore gained increasing attention, but the precise measurement of their invasive capacity and the evaluation of potential treatment effects constitute a challenge that needs to be addressed. This study used a novel in vitro invasion assay based on the breakdown of transepithelial electrical resistance to determine the course of fibroblast invasion into extracellular matrix. Methods A matrix-associated transepithelial resistance invasion (MATRIN) assay was used to assess SFs from patients with RA in comparison with SFs from patients with osteoarthritis (OA). The SFs were grown on a commercially available collagen mix that was placed onto the upper side of a Transwell polycarbonate membrane. In addition, freshly isolated cartilage extracts were studied to assess the conditions in vivo. Under this membrane, a monolayer of MDCK-C7 cells was seeded to create a high electrical resistance. Results Invasion of fibroblasts into the matrix affected the integrity of the MDCK-C7 monolayer and led to a measurable decrease and subsequent breakdown of electrical resistance. Unlike in the assay with OASFs, which did not achieve a breakdown of resistance up to 72 hours, RASFs exhibited a pronounced invasiveness in this assay, with a 50% breakdown after 42 hours. Treatment of fibroblasts with either a matrix metalloproteinase inhibitor or antibodies against ,1 integrin significantly reduced the invasiveness of RASFs. Conclusion The MATRIN assay is a valuable and sensitive biologic assay system that can be used to determine precisely the invasive potential of RASFs in vitro, and thus would be suitable for screening anti-invasion compounds. [source]


Cadherin 11 promotes invasive behavior of fibroblast-like synoviocytes

ARTHRITIS & RHEUMATISM, Issue 5 2009
Hans P. Kiener
Objective To define the expression pattern of cadherin 11 in the destructive pannus tissue of patients with rheumatoid arthritis, and to determine whether cadherin 11 expression in fibroblast-like synoviocytes controls their invasive capacity. Methods Cadherin 11 expression in rheumatoid synovial tissue was evaluated using immunohistochemistry. To examine the role of cadherin 11 in regulating the invasive behavior of fibroblast-like synoviocytes, we generated L cell clones expressing wild-type cadherin 11, mutant cadherin 11, and empty vector,transfected controls. The invasive capacity of L cell transfectants and cultured fibroblast-like synoviocytes treated with a blocking cadherin 11,Fc fusion protein or control immunoglobulin was determined in Matrigel invasion assays. Results Immunohistochemical analysis revealed that cadherin 11 is abundantly expressed in cells at the cartilage,pannus junction in rheumatoid synovitis. Assays to determine invasion demonstrated a 2-fold increased invasive capacity of cadherin 11,transfected L cells compared with L cells transfected with E-cadherin or control vector. The invasive behavior of L cells stably transfected with a cadherin 11 construct that lacked the juxtamembrane cytoplasmic domain was diminished to the level of vector control L cells. Furthermore, treatment with the cadherin 11,Fc fusion protein diminished the invasive capacity of fibroblast-like synoviocytes. Conclusion The results of these in vitro studies implicate a role for cadherin 11 in promoting cell invasion and contribute insight into the invasive nature of fibroblast-like synoviocytes in chronic synovitis and rheumatoid arthritis. [source]


The src-family kinase inhibitor PP2 suppresses the in vitro invasive phenotype of bladder carcinoma cells via modulation of Akt,

BJU INTERNATIONAL, Issue 3 2005
George J. Chiang
OBJECTIVE To evaluate PP2 as a modulator of the cadherin/catenin complex in late-stage bladder carcinoma cells, and to assess its potential invasion-suppressor activity in this model. MATERIALS AND METHODS A panel of five human bladder carcinoma cells, characterizing late-stage disease, was used to determine the concentration for 50% inhibition of PP2 in cell-proliferation assays. Modulation of cadherin/catenin expression by PP2 was determined in Western blot analysis, with an assessment of the activation status of mitogen-activated protein kinase and Akt signalling pathways. Altered invasive capacity linked to these variables was determined in standard in vitro invasion assays. RESULTS PP2 elicited concentration-dependent growth inhibition in all bladder cell lines within the panel, with growth suppression recorded at 10,35 µmol/L PP2. Distinct morphological changes were recorded in cell lines exposed to PP2, accompanied by up-regulation of plakoglobin expression in a subset of lines. Exposure of cells to PP2 resulted in inactivation of Akt in all cells and a concomitant reduction in in vitro invasive capacity. CONCLUSIONS These results show that PP2 inhibits bladder carcinoma cell growth and can modulate plakoglobin expression in a subset of cell lines. In addition, PP2 can suppress the in vitro invasive capacity of bladder carcinoma cells by modulating the activation status of Akt. [source]


Hypermethylation in promoter region of E-cadherin gene is associated with tumor dedifferention and myometrial invasion in endometrial carcinoma

CANCER, Issue 4 2003
Ph.D., Tsuyoshi Saito M.D.
Abstract BACKGROUND Loss of E-cadherin expression is associated with aberrant 5, CpG island methylation in various tumors. METHODS The authors analyzed the methylation status and immunohistochemical expression of E-cadherin in 142 endometrial tissues, consisting of 21 normal endometria, 17 endometrial hyperplasias, and 104 endometrial carcinomas. RESULTS All normal endometria and endometrial hyperplasias showed positive staining of E-cadherin, and methylation of the E-cadherin gene was not detected in any samples. In endometrial carcinoma, the positive ratio of methylation was higher and was associated with tumor dedifferention and myometrial invasion. In G1 endometrial adenocarcinomas, 66.7% showed positive staining and 33.3% showed heterogeneous staining. Methylation of the E-cadherin gene was detected in 15.6%. In G2 tumors, 19.0% showed positive staining, 69.0% showed heterogeneous staining and 11.9% showed negative staining. Methylation of the E-cadherin gene was found in 50.0%. In G3 tumors, 9.1% showed positive staining, 54.5% showed heterogeneous staining and 36.3% showed negative staining. Methylation of the E-cadherin gene was found in 81.8% of the tumors. Of the samples with no-myometrial invasion, 23.1% had methylation. In those with invasion in less than half of the myometrium, 28.6% did and in those with invasion of half or more of the myometrium, 55.6% had methylation. Of samples that did not have lymph node metastasis, 33.7% had methylation, whereas of samples that had lymph node metastasis, 60.0% had methylation. CONCLUSIONS This is the first report to analyze methylation of the E-cadherin gene promoter of endometrial carcinoma and the evidence suggests that methylation of the E-cadherin gene occurs in association with the acquisition of invasive capacity. Cancer 2003;97:1002,9. © 2003 American Cancer Society. DOI 10.1002/cncr.11157 [source]