Tenascin mediates human glioma cell migration and modulates cell migration on fibronectin

1996 ◽  
Vol 109 (3) ◽  
pp. 643-652 ◽  
Author(s):  
E.I. Deryugina ◽  
M.A. Bourdon
Keyword(s):  
Cell Migration ◽  
Tumor Cell ◽  
Cell Morphology ◽  
Radial Distance ◽  
Tumor Cell Migration ◽  
Migration Rates ◽  
Cell Responses ◽  
Coated Surfaces ◽  
Blocking Antibodies

The role of tenascin in mediating tumor cell migration was studied using two cell migration models. In migration/invasion Transwell assays U251.3 glioma cells rapidly migrated through the 8 mu m pore size membranes onto tenascin- and fibronectin-coated surfaces. In this assay the number of cells migrating onto tenascin was 52.2 +/- 9.6% greater than on fibronectin within 4 hours. To assess cell migration rates and cell morphology, U251.3 migration was examined in a two-dimension spheroid outgrowth assay. The radial distance migrated by U251.3 cells from tumor spheroids was found to be 53.8 +/- 4.9% greater on tenascin than on fibronectin. Cells migrating on tenascin display a very motile appearance, while cells migrating on fibronectin spread and maintain close intercellular contacts. Cell migration in the presence of integrin blocking antibodies demonstrated that migration on tenascin and fibronectin is mediated by distinct integrins, alpha2beta1 and alphavbeta5/alphavbeta3, respectively. Since tenascin is coexpressed in malignant tumor matrices with fibronectin, we assessed the effects of tenascin on U251.3 cell migration mediated by fibronectin. Tenascin was found to provide a positive effect on fibronectin-mediated migration by altering cell morphology and enhancing cell motility. These effects of tenascin on fibronectin-mediated cell migration were inhibited by blocking beta1 and alpha2beta1 integrins. The results suggest that tenascin may play a significant role in promoting tumor cell migration and invasiveness by modulating cell responses to normal matrix components.

The Cytoplasmic Domain of Tissue Factor Inhibits Migration and Enhances Adhesion of Human Breast Cancer Cells.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1939-1939
Author(s):  
Xiaofeng Jiang ◽  
Tracee S. Panetti ◽  
Michael E. Bromberg
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Tumor Cell ◽  
Cell Line ◽  
Human Breast Cancer ◽  
Cytoplasmic Domain ◽  
Human Breast ◽  
Tumor Cell Migration ◽  
Mcf 7

Abstract Tissue factor (TF) is a 47 kDa transmembrane glycoprotein that when complexed with its cofactor, factor VIIa (FVIIa), initiates blood coagulation. Apart from hemostasis, TF has been shown to have roles in cellular signaling, development, inflammation, metastasis and angiogenesis. We showed previously that both the cytoplasmic and extracellular domains of TF are required for the full metastatic effect of TF. Recently, we showed that TF-FVIIa-FXa complex induces cellular signaling in human breast cancer cells and is associated with enhanced cell migration and prevention of apoptosis. However, the role of the cytoplasmic domain of TF in tumor cell function is not fully known. In the present study, the role of the cytoplasmic domain of TF in cell migration and adhesion was investigated using the Adr-MCF-7 cell line, a multidrug resistant subline of the human breast cancer cell line, MCF-7. The Adr-MCF-7 cell line has high endogenous expression of TF and expression of PAR1 and PAR2. Adr-MCF-7 cells were retrovirally transfected with either a cDNA construct encoding a FLAG epitope tag fused to the transmembrane and cytoplasmic domains of TF (known as FLAG-TFCD) or vector (LXSN) alone as a control, and stable, polyclonal cell lines selected using G418. Expression of the FLAG-TFCD construct was verified by RT-PCR, Western blot analysis and flow cytometry. To test the effect of overexpression of the FLAG-TFCD construct on cell motility a modified Boyden chamber chemotaxis assay was used. The control LXSN cell line had a nearly 9 fold increase in cell migration [33.5± 3.2 cells/hpf (mean± SEM)]using the combination of rFVIIa (10 nM) and FX (150 nM) as the chemoattractant compared with 0.1% bovine serum albumin (BSA) [3.9± 1.2 cells/hpf]. In contrast, the FLAG-TFCD cell line had no increase in migration of using the combination of rFVIIa and FX [6.6± 0.57 cells/hpf] compared with BSA [5.4± 0.67 cells/hpf]. We then examined the ability of the transfected cell lines to adhere to type IV collagen. The number of adherent cells for the transfected cell line, FLAG-TFCD, was nearly 3 fold higher than that for the LXSN line using a colorimetric MTS assay (0.295± 0.041 vs 0.119± 0.011). Moreover, treatment of the FLAG-TFCD cells with the combination of rFVIIa and FX increased the adhesion by nearly 2 fold compared with untreated FLAG-TFCD cells (0.561±0.055 vs 0.296±0.044). In summary, overexpression of TF cytoplasmic domain leads to inhibition of tumor cell migration and enhancement of cell adhesion and potentially acts as a dominant negative in these cellular processes. These data suggest that a function of the cytoplasmic domain of TF in metastasis is to regulate tumor cell migration and adhesion.

scholarly journals The Role of Calmodulin in Tumor Cell Migration, Invasiveness, and Metastasis

2020 ◽  
Vol 21 (3) ◽  
pp. 765 ◽  
Author(s):  
Antonio Villalobo ◽  
Martin W. Berchtold
Keyword(s):  
Cell Migration ◽  
Tumor Cell ◽  
Small Gtpases ◽  
Vast Number ◽  
Mesenchymal Transition ◽  
Tumor Cell Migration ◽  
Iq Motif ◽  
Metastasis Development ◽  
Cell Invasiveness

Calmodulin (CaM) is the principal Ca2+ sensor protein in all eukaryotic cells, that upon binding to target proteins transduces signals encoded by global or subcellular-specific changes of Ca2+ concentration within the cell. The Ca2+/CaM complex as well as Ca2+-free CaM modulate the activity of a vast number of enzymes, channels, signaling, adaptor and structural proteins, and hence the functionality of implicated signaling pathways, which control multiple cellular functions. A basic and important cellular function controlled by CaM in various ways is cell motility. Here we discuss the role of CaM-dependent systems involved in cell migration, tumor cell invasiveness, and metastasis development. Emphasis is given to phosphorylation/dephosphorylation events catalyzed by myosin light-chain kinase, CaM-dependent kinase-II, as well as other CaM-dependent kinases, and the CaM-dependent phosphatase calcineurin. In addition, the role of the CaM-regulated small GTPases Rac1 and Cdc42 (cell division cycle protein 42) as well as CaM-binding adaptor/scaffold proteins such as Grb7 (growth factor receptor bound protein 7), IQGAP (IQ motif containing GTPase activating protein) and AKAP12 (A kinase anchoring protein 12) will be reviewed. CaM-regulated mechanisms in cancer cells responsible for their greater migratory capacity compared to non-malignant cells, invasion of adjacent normal tissues and their systemic dissemination will be discussed, including closely linked processes such as the epithelial–mesenchymal transition and the activation of metalloproteases. This review covers as well the role of CaM in establishing metastatic foci in distant organs. Finally, the use of CaM antagonists and other blocking techniques to downregulate CaM-dependent systems aimed at preventing cancer cell invasiveness and metastasis development will be outlined.

scholarly journals MEKK1 Regulates Chemokine Expression in Mammary Fibroblasts: Implications for the Breast Tumor Microenvironment

2021 ◽  
Vol 11 ◽  
Author(s):  
Saverio Gentile ◽  
Najmeh Eskandari ◽  
Michael A. Rieger ◽  
Bruce D. Cuevas
Keyword(s):  
Gene Expression ◽  
Cell Migration ◽  
Tumor Microenvironment ◽  
Tumor Cell ◽  
Breast Tumor ◽  
Cell Function ◽  
Breast Tumor Cell ◽  
Tumor Cell Migration ◽  
Stroma Cell

Breast tumors contain both transformed epithelial cells and non-transformed stroma cells producing secreted factors that can promote metastasis. Previously, we demonstrated that the kinase MEKK1 regulates cell migration and gene expression, and that transgene-induced breast tumor metastasis is markedly inhibited in MEKK1-deficient mice. In this report, we examined the role of MEKK1 in stroma cell gene expression and the consequent effect on breast tumor cell function. Using a heterotypic cell system to quantify the effect of stroma cells on breast tumor cell function, we discovered that MEKK1−/− fibroblasts are significantly less effective at inducing tumor cell invasion than MEKK1+/+ fibroblasts. Expression array analysis revealed that both baseline and tumor cell-induced expression of the chemokines CCL3, CCL4, and CCL5 were markedly reduced in MEKK1−/− mammary fibroblasts. By focusing on the role of MEKK1 in CCL5 regulation, we discovered that MEKK1 kinase activity promotes CCL5 expression, and inactive mutant MEKK1 strongly inhibits CCL5 transcription. CCL5 and the other MEKK1-dependent chemokines are ligands for the GPCR CCR5, and we show that the CCR5 antagonist Maraviroc strongly inhibits fibroblast-induced tumor cell migration. Finally, we report that fibroblast growth factor 5 (FGF-5) is secreted by MDA-MB 231 cells, that FGF-5 activates MEKK1 effectors ERK1/2 and NFκB in fibroblasts, and that chemical inhibition of NFκB inhibits CCL5 expression. Our results suggest that MEKK1 contributes to the formation of a breast tumor microenvironment that supports metastasis by promoting expression of stroma cell chemokine genes in response to tumor cell-induced paracrine signaling.

Abstract 470: Role of Fli1 in hematopoietic stem cell-derived fibroblast promotion of tumor cell migration and invasion

2011 ◽  
Author(s):  
Lindsay T. McDonald ◽  
Daniel J. Neitzke ◽  
Victoria J. Findlay ◽  
David P. Turner ◽  
Patricia M. Watson ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Migration ◽  
Tumor Cell ◽  
Hematopoietic Stem Cell ◽  
Migration And Invasion ◽  
Hematopoietic Stem ◽  
Cell Migration And Invasion ◽  
Tumor Cell Migration

scholarly journals Id1 Promotes Tumor Cell Migration in Nonsmall Cell Lung Cancers

2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
Raka Bhattacharya ◽  
Jeanne Kowalski ◽  
Allison R. Larson ◽  
Malcolm Brock ◽  
Rhoda M. Alani
Keyword(s):  
Cell Migration ◽  
Tumor Cell ◽  
Constitutive Expression ◽  
Tumor Cell Growth ◽  
Rt Pcr ◽  
Primary Tumors ◽  
Lung Cancers ◽  
Tumor Cell Migration ◽  
Helix Loop Helix

Id1, which belongs to the Id family of helix-loop-helix transcription factors has been most associated with tumor progression and metastatsis; however, its significance in lung cancers has not been extensively explored. Here we seek to evaluate the expression of Id1 in a pilot study of nonsmall-cell lung cancers (NSCLCs) and determine its diagnostic and functional significance in these tumors. Paired normal and malignant lung tissues as well as a panel of NSCLC primary tumors and cell lines were evaluated for Id1 expression using Western blotting and quantitative RT-PCR. Functional assays were performed to evaluate the role of Id1 in tumor cell growth, migration and progression. We find Id1 expression is upregulated in squamous cell carcinoma when compared to adenocarcinoma of the lung and that expression of Id1 versus the normal control is variable in NSCLCs. We also note that Id1 expression in NSCLC cells is largely growth factor dependant and constitutive expression of Id1 in NSCLC cells significantly increases tumor cell migration without affecting cell proliferation. We conclude that Id1, as a mediator of tumor cell migration, may be an indicator of aggressive potential in nonsmall-cell lung cancers.

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