Extracellular matrix-modulated differential invasion of human meningioma cell lines in vitro

1999 ◽  
Vol 263 (2-3) ◽  
pp. 214-216 ◽  
Author(s):  
Harcharan K Rooprai ◽  
Krishanthi Liyanage ◽  
Susan F.D Robinson ◽  
Apsara Kandanearatchi ◽  
Andrew F Dean ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Lines ◽  
Human Meningioma ◽  
Meningioma Cell

scholarly journals EXTH-64. SMALL GTPASES IN MENINGIOMAS: PROLIFERATION, MIGRATION, SURVIVAL, POTENTIAL TREATMENT AND INTERACTIONS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii101-ii101
Author(s):  
Christoph Kesseler ◽  
Julian Kahr ◽  
Natalie Waldt ◽  
Nele Stroscher ◽  
Josephine Liebig ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cell Lines ◽  
Small Gtpases ◽  
Potential Treatment ◽  
Rock Inhibitor ◽  
Meningioma Cell ◽  
And Migration ◽  
Proliferation And Migration

Abstract PURPOSE To evaluate the role of the small GTPases RhoA, Rac1 and Cdc42 in meningiomas as therapeutic targets and their interactions in meningiomas. EXPERIMENTAL DESIGN We analyzed expression of GTPases in human meningioma samples and meningioma cell lines of various WHO grades. Malignant IOMM-Lee meningioma cells were used to generate shRNA mediated knockdowns of GTPases RhoA, Rac1 or Cdc42 and to study knockdown effects on proliferation and migration, as well as analysis of cell morphology by confocal microscopy. The same tests were used to investigate effects of the two inhibitors Fasudil and EHT-1864 of malignant IOMM-Lee, KT21 and benign Ben-Men cells and the effects of these drugs on IOMM-Lee knockdown cells. The effects of GTPase knockdowns and Fasudil treatment were studied in terms of overall survival by intracranial xenografts of mice. Potential interactions of GTPases regarding NF2, mTOR and FAK-Paxillin were examined. RESULTS Small GTPases were upregulated in meningiomas of higher tumor grades. Reduced proliferation and migration could be achieved by GTPase knockdown in IOMM-Lee cells. Additionally, the ROCK-inhibitor Fasudil and Rac1-inhibitor EHT-1864 reduced proliferation in different meningioma cell lines and reduced proliferation and migration independent of GTPase knockdowns/status. Moreover, overall survival in vivo could also be increased by knockdowns of RhoA and Rac1 as well as Fasudil treatment. GTPase expression was affected dependent on the NF2 status but effects were not very distinct, indicating that NF2 is not strongly involved in GTPase regulation in meningiomas. In terms of mTOR and FAK-Paxillin signaling, each GTPase changes those pathways in a different manner. CONCLUSION Small GTPases are important effectors in meningioma proliferation and migration in vitro as well as survival in vivo and their inhibition should be considered as potential treatment option.

scholarly journals Impact of extracellular matrix properties on neuroblastoma genomic heterogeneity

2020 ◽  
Author(s):  
Amparo López-Carrasco ◽  
Susana Martín-Vañó ◽  
Rebeca Burgos-Panadero ◽  
Ezequiel Monferrer ◽  
Ana P Berbegall ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
High Risk ◽  
Cell Lines ◽  
Neuroblastoma Cell ◽  
Chromosome 9 ◽  
Future Research ◽  
Knock Out ◽  
Specific Distribution

Abstract Background Increased tissue stiffness is a common feature of malignant solid tumors, often associated with metastasis and poor patient outcomes. Vitronectin, as an extracellular matrix anchorage glycoprotein related to a stiff matrix, is present in a particularly increased quantity and specific distribution in high-risk neuroblastoma. Furthermore, as cells can sense and transform the proprieties of the extracellular matrix into chemical signals through mechanotransduction, genotypic changes related to stiffness are possible. Methods We have applied high density SNPa and NGS techniques to in vivo and in vitro models (orthotropic xenograft vitronectin knock-out mice and 3D bioprinted hydrogels with different stiffness) using two representative neuroblastoma cell lines (the MYCN amplified SK-N-BE(2) and the ALK mutated SH-SY5Y), to discern how tumor genomics patterns and clonal heterogeneity of both cell lines are affected. Results We describe a remarkable subclonal selection of some genomic aberrations in SK-N-BE(2) cells grown in knock-out vitronectin xenograft mice that also emerged when cultured for long times in stiff hydrogels. Specially, we detected an enlarged subclonal cell population with chromosome 9 aberrations in both models. Similar abnormalities were found in human high-risk neuroblastoma with MYCN amplification. Genomics of the SH-SY5Y cell line remained stable when cultured in both models. Conclusions Focus on heterogeneous intratumor segmental chromosome aberrations and mutations, as a mirror image of tumor microenvironment, is a vital area of future research.

scholarly journals Aminolevulinic Acid-Mediated Photodynamic Therapy of Human Meningioma: An in Vitro Study on Primary Cell Lines

2015 ◽  
Vol 16 (12) ◽  
pp. 9936-9948 ◽  
Author(s):  
Mustafa El-Khatib ◽  
Carolin Tepe ◽  
Brigitte Senger ◽  
Maxine Dibué-Adjei ◽  
Markus Riemenschneider ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Cell Lines ◽  
Aminolevulinic Acid ◽  
In Vitro Study ◽  
Vitro Study ◽  
Primary Cell ◽  
Human Meningioma ◽  
Primary Cell Lines

Lysyl Oxidase, Cellular Senescence and Tumor Suppression

1997 ◽  
Vol 17 (4) ◽  
pp. 409-414 ◽  
Author(s):  
Rashmi Sharma ◽  
Jeffrey A. Kramer ◽  
Stephen A. Krawetz
Keyword(s):  
Extracellular Matrix ◽  
Cell Lines ◽  
Cellular Senescence ◽  
Tumor Suppression ◽  
Replicative Senescence ◽  
Lysyl Oxidase ◽  
Normal Fibroblast ◽  
Northern Hybridization ◽  
Type Iii Collagen

Replicative senescence may provide a mechanism of tumor suppression and tumor suppressor genes of the extracellular matrix, like lysyl oxidase, may play a role in cellular senescence. To test this hypothesis and determine whether the extracellular matrix may serve as a marker, the steady-state levels of human lysyl oxidase, α-I type III collagen and β-actin transcripts were assessed in various cell lines during in vitro passge. Northern hybridization analysis showed a significant increase in the levels of progeria fibroblast extracellular matrix mRNAs immediately preceding senescence. The levels of these mRNAs were unaffected in age-matched normal fibroblast and fetal fibroblast cell lines.

scholarly journals Differential attachment of human neoplastic B cells to purified extracellular matrix molecules

Blood ◽  
1994 ◽  
Vol 83 (6) ◽  
pp. 1586-1594 ◽  
Author(s):  
D Segat ◽  
C Pucillo ◽  
G Marotta ◽  
R Perris ◽  
A Colombatti
Keyword(s):  
Extracellular Matrix ◽  
Cell Adhesion ◽  
B Cells ◽  
B Cell ◽  
Cell Lines ◽  
Philadelphia Chromosome ◽  
Maturation State ◽  
Neoplastic Lymphocytes

Recirculation of normal and neoplastic lymphocytes occurs via binding to the endothelial luminar surface, followed by extravasation and the subsequent interaction of the cells with components of the underlying basement membrane and stromal extracellular matrix (ECM). To identify matrix constituents that could be involved in the tissue dissemination of neoplastic B cells, we have examined the ability of three lymphoma B- cell lines and one Philadelphia chromosome (Ph1)-positive cell line established from the lymphoid transformation of a chronic myeloid leukemia (CML) to adhere to a range of purified ECM molecules. Immunophenotyping with a panel of markers suggested that the lines derived from cells that had undergone transformation at distinct stages of B-cell maturation. The four cell lines displayed a differential ability to adhere to the ECM molecules tested. BV-173, Ci-1, and Sc-1 cells attached to various degrees to fibronectin (FN). Ri-1, Ci-1, and Sc-1 cells attached to human laminin (LN) variants, whereas only Ci-1 and Sc-1 cells showed some affinity for collagen (Col) type VI. All four cell lines interacted with fibrillar Col I, but only BV-173 and Ri- 1 cells attached to fibrillar Col III. The subendothelial Col VIII only was active as a substratum for BV-173 cells. In all cases, cells bound to fibrillar collagens when they were assembled into polymeric fibrils, and were incapable of adhering to monomeric and denatured collagen. In contrast to cell adhesion to FN and LN, which showed a plateau at high substrate concentrations, adhesion to fibrillar Col I reached a peak at intermediary concentrations and decreased thereafter, suggesting that cells respond to a definite macromolecular arrangement of collagenous fibrils. Adhesion to individual ECM molecules was not directly correlated with the apparent maturation state of the cells, nor with the relative density of known ECM receptors. Taken together, these results suggest that interaction of neoplastic B cells with selected matrix components may influence their dispersion throughout tissues. We further suggest that the use of quantitative cell adhesion assays in vitro may provide means of defining the behavioral traits of neoplastic B cells in vivo.

scholarly journals Phenotypic heterogeneity among stromal cell lines from mouse bone marrow disclosed in their extracellular matrix composition and interactions with normal and leukemic cells

Blood ◽  
1985 ◽  
Vol 66 (2) ◽  
pp. 447-455 ◽  
Author(s):  
D Zipori ◽  
J Toledo ◽  
K von der Mark
Keyword(s):  
Bone Marrow ◽  
Extracellular Matrix ◽  
Cell Line ◽  
Cell Lines ◽  
Stromal Cell ◽  
Leukemic Cells ◽  
Matrix Composition ◽  
Mouse Bone Marrow ◽  
Type I

Abstract Study of a series of stromal cell lines from mouse bone marrow (MBA) verified and extended their classification as phenotypically distinct subtypes. Production of extracellular matrix proteins was examined using specific antibodies. Fibronectin and laminin were detected in all of the cell lines tested, yet 14F1.1 adipocytes exhibited particularly prominent extracellular deposition. This cell line and MBA-13.2 cells were positive to both collagen types I and IV, whereas MBA-1 and MBA- 2.1 were stained with anticollagen type I antibodies only. Coculture experiments revealed differences among the lines in their effects on normal myeloid cells and leukemic cell lines. In promoting the in vitro accumulation of myeloid progenitors (CFU-C), 14F1.1 cells surpassed the others. The MBA-2.1 cell line was particularly inhibitory to MPC-11 plasmacytoma and Friend erythroleukemia cells. However, the latter were refractory to other stromal cell lines, whereas MPC-11 cells were inhibited to various degrees by virtually all of the cell lines. Physical separation between the interacting cells reduced the inhibition in some but not all cases, and no inhibitory activity was detected in conditioned media. The MBA-13 stromal cells synergistically promoted the differentiation of dimethylsulfoxide (Me2SO)-induced Friend erythroleukemia. The latter cells themselves, at high concentrations, as well as some of the stromal cell lines and unrelated adherent cells, antagonized the Me2SO effect, revealing possible reversible stages in the Friend cell differentiation pathway.

scholarly journals EXTH-63. IN VITRO DRUG SCREENING BASED ON IN SILICO DATA IDENTIFIES NEW THERAPEUTIC AGENTS FOR AGGRESSIVE MENINGIOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii101-ii101
Author(s):  
Gerhard Jungwirth ◽  
Junguo Cao ◽  
Tao Yu ◽  
Rolf Warta ◽  
Andreas Unterberg ◽  
...  
Keyword(s):  
Cell Lines ◽  
Drug Screening ◽  
In Silico ◽  
Treatment Options ◽  
Area Under The Curve ◽  
Microarray Dataset ◽  
Phase Iii ◽  
Drug Candidates ◽  
Meningioma Cell

Abstract The mainstay of treatment for progressive or recurrent meningiomas is surgery and/or radiotherapy. Patients with refractory cancer might benefit from systemic treatment options. However, to date, no effective chemotherapy is available for these patients. For this reason, novel inhibitors for the treatment of aggressive meningiomas are urgently needed. Therefore, we used our previously published Affymetrix microarray dataset (GSE74385) consisting of 62 meningiomas enriched with 28 WHO°III MGMs to screen substantially expressed genes that can be targeted by available inhibitors. For each targeted gene, three compounds were selected based on their clinical development. This filter process resulted in 107 drugs targeting 57 different genes. Most compounds were oncology-related (n = 94, 88%) with the remaining compounds being non-oncology agents (n = 13, 12%). Thereafter, a 2-stage screening strategy was employed. First, drugs were screened at a single dose (2.5 µM) in two malignant meningioma cell lines (NCH93 and IOMM-Lee) with CellTiter-Glo (Promega). Only drugs resulting in a cell viability of 50% or less of either cell line were considered for further validation. Remaining drug candidates (n = 33) exclusively belonged to the oncology-related group, consisting of 4 FDA-approved antineoplastic drugs (12%). The other drugs are currently tested in clinical trials (24% in phase III, 39% in phase II, and 24% in phase I). Drug candidates were further analyzed in a six-point dose-response scheme ranging from 0.1 nM to 10 µM in three meningioma cell lines (Ben-Men-1, NCH93, IOMM-Lee). The top 5 drugs were selected based on the lowest mean of z-transformed area under the curve. Resulting drugs and corresponding targets are: OTSSP167 (MELK), Panobinostat (HDAC), Picropodophyllin (IGF-1R), KPT-9274 (PAK4 and NAMPT), and BI-2536 (PLK1). Taken together, our drug screening approach utilized in silico data to identify potential inhibitors for the treatment of aggressive meningiomas warranting further preclinical investigation.

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