scholarly journals LOXL3 Silencing Affected Cell Adhesion and Invasion in U87MG Glioma Cells

2021 ◽  
Vol 22 (15) ◽  
pp. 8072
Author(s):  
Talita de S. Laurentino ◽  
Roseli da S. Soares ◽  
Antonio M. Lerario ◽  
Suely K. N. Marie ◽  
Sueli M. Oba-Shinjo
Keyword(s):  
Cell Adhesion ◽  
Tumor Cell ◽  
Cell Invasion ◽  
Cellular Localization ◽  
Lysyl Oxidase ◽  
In Silico Analysis ◽  
Rna Seq ◽  
Matrix Cell ◽  
Proliferation And Metastasis ◽  
Focal Adhesion Turnover

Lysyl oxidase-like 3 (LOXL3), belonging to the lysyl oxidase family, is responsible for the crosslinking in collagen or elastin. The cellular localization of LOXL3 is in the extracellular space by reason of its canonical function. In tumors, the presence of LOXL3 has been associated with genomic stability, cell proliferation, and metastasis. In silico analysis has shown that glioblastoma was among tumors with the highest LOXL3 expression levels. LOXL3 silencing of U87MG cells by siRNA led to the spreading of the tumor cell surface, and the transcriptome analysis of these cells revealed an upregulation of genes coding for extracellular matrix, cell adhesion, and cytoskeleton components, convergent to an increase in cell adhesion and a decrease in cell invasion observed in functional assays. Significant correlations of LOXL3 expression with genes coding for tubulins were observed in the mesenchymal subtype in the TCGA RNA-seq dataset of glioblastoma (GBM). Conversely, genes involved in endocytosis and lysosome formation, along with MAPK-binding proteins related to focal adhesion turnover, were downregulated, which may corroborate the observed decrease in cell viability and increase in the rate of cell death. Invasiveness is a major determinant of the recurrence and poor outcome of GBM patients, and downregulation of LOXL3 may contribute to halting the tumor cell invasion.

scholarly journals Dissecting the Invasion-Associated Long Non-coding RNAs Using Single-Cell RNA-Seq Data of Glioblastoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Bo Pang ◽  
Fei Quan ◽  
Yanyan Ping ◽  
Jing Hu ◽  
Yujia Lan ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Single Cell ◽  
Cell Invasion ◽  
Molecular Mechanisms ◽  
Single Cells ◽  
Tumor Cell Invasion ◽  
Rna Seq ◽  
Validation Data ◽  
Invasion And Migration ◽  
Non Coding Rnas

Glioblastoma (GBM) is characterized by rapid and lethal infiltration of brain tissue, which is the primary cause of treatment failure and deaths for GBM. Therefore, understanding the molecular mechanisms of tumor cell invasion is crucial for the treatment of GBM. In this study, we dissected the single-cell RNA-seq data of 3345 cells from four patients and identified dysregulated genes including long non-coding RNAs (lncRNAs), which were involved in the development and progression of GBM. Based on co-expression network analysis, we identified a module (M1) that significantly overlapped with the largest number of dysregulated genes and was confirmed to be associated with GBM invasion by integrating EMT signature, experiment-validated invasive marker and pseudotime trajectory analysis. Further, we denoted invasion-associated lncRNAs which showed significant correlations with M1 and revealed their gradually increased expression levels along the tumor cell invasion trajectory, such as VIM-AS1, WWTR1-AS1, and NEAT1. We also observed the contribution of higher expression of these lncRNAs to poorer survival of GBM patients. These results were mostly recaptured in another validation data of 7930 single cells from 28 GBM patients. Our findings identified lncRNAs that played critical roles in regulating or controlling cell invasion and migration of GBM and provided new insights into the molecular mechanisms underlying GBM invasion as well as potential targets for the treatment of GBM.

scholarly journals A Drosophila RNAi screen reveals conserved glioblastoma-related adhesion genes that regulate collective cell migration

2021 ◽  
Author(s):  
Nirupama Kotian ◽  
Katie M Troike ◽  
Kristen N Curran ◽  
Justin D Lathia ◽  
Jocelyn A McDonald
Keyword(s):  
Cell Migration ◽  
Cell Adhesion ◽  
Cell Invasion ◽  
Brain Parenchyma ◽  
Cell Junction ◽  
Collective Cell Migration ◽  
Border Cells ◽  
Bioinformatics Analyses ◽  
Border Cell ◽  
Matrix Cell

Abstract Migrating cell collectives are key to embryonic development but also contribute to invasion and metastasis of a variety of cancers. Cell collectives can invade deep into tissues, leading to tumor progression and resistance to therapies. Collective cell invasion is also observed in the lethal brain tumor glioblastoma, which infiltrates the surrounding brain parenchyma leading to tumor growth and poor patient outcomes. Drosophila border cells, which migrate as a small cell cluster in the developing ovary, are a well-studied and genetically accessible model used to identify general mechanisms that control collective cell migration within native tissue environments. Most cell collectives remain cohesive through a variety of cell-cell adhesion proteins during their migration through tissues and organs. In this study, we first identified cell adhesion, cell matrix, cell junction, and associated regulatory genes that are expressed in human brain tumors. We performed RNAi knockdown of the Drosophila orthologs in border cells to evaluate if migration and/or cohesion of the cluster was impaired. From this screen, we identified eight adhesion-related genes that disrupted border cell collective migration upon RNAi knockdown. Bioinformatics analyses further demonstrated that subsets of the orthologous genes were elevated in the margin and invasive edge of human glioblastoma patient tumors. These data together show that conserved cell adhesion and adhesion regulatory proteins with potential roles in tumor invasion also modulate collective cell migration. This dual screening approach for adhesion genes linked to glioblastoma and border cell migration thus may reveal conserved mechanisms that drive collective tumor cell invasion.

scholarly journals Characterization of a synthetic peptide from type IV collagen that promotes melanoma cell adhesion, spreading, and motility.

1990 ◽  
Vol 111 (1) ◽  
pp. 261-270 ◽  
Author(s):  
M K Chelberg ◽  
J B McCarthy ◽  
A P Skubitz ◽  
L T Furcht ◽  
E C Tsilibary
Keyword(s):  
Cell Adhesion ◽  
Tumor Cell ◽  
Melanoma Cell ◽  
Cell Invasion ◽  
Synthetic Peptide ◽  
Type Iv Collagen ◽  
Cell Types ◽  
Tumor Cell Invasion ◽  
Type Iv

The adhesion and motility of tumor cells on basement membranes is a central consideration in tumor cell invasion and metastasis. Basement membrane type IV collagen directly promotes the adhesion and migration of various tumor cell types in vitro. Our previous studies demonstrated that tumor cells adhered and spread on surfaces coated with intact type IV collagen or either of the two major enzymatically purified domains of this protein. Only one of these major domains, the pepsin-generated major triple helical fragment, also supported tumor cell motility in vitro, implicating the involvement of the major triple helical region in type IV collagen-mediated tumor cell invasion in vivo. The present studies extend our previous observations using a synthetic peptide approach. A peptide, designated IV-H1, was derived from a continuous collagenous region of the major triple helical domain of the human alpha 1(IV) chain. This peptide, which has the sequence GVKGDKGNPGWPGAP, directly supported the adhesion, spreading, and motility of the highly metastatic K1735 M4 murine melanoma cell line, as well as the adhesion and spreading of other cell types, in a concentration-dependent manner in vitro. Furthermore, excess soluble peptide IV-H1, or polyclonal antibodies directed against peptide IV-H1, inhibited type IV collagen-mediated melanoma cell adhesion, spreading, and motility, but had no effect on these cellular responses to type I collagen. The full complement of cell adhesion, spreading, and motility promoting activities was dependent upon the preservation of the three prolyl residues in the peptide IV-H1 sequence. These studies indicate that peptide IV-H1 represents a cell-specific adhesion, spreading, and motility promoting domain that is active within the type IV collagen molecule.

Disruption of STAT3 signaling leads to tumor cell invasion through alterations of homotypic cell–cell adhesion complexes

Oncogene ◽  
2004 ◽  
Vol 23 (19) ◽  
pp. 3317-3327 ◽  
Author(s):  
Christine Rivat ◽  
Olivier De Wever ◽  
Erik Bruyneel ◽  
Marc Mareel ◽  
Christian Gespach ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Tumor Cell ◽  
Cell Invasion ◽  
Tumor Cell Invasion ◽  
Stat3 Signaling ◽  
Cell Cell

scholarly journals α1 and α2 Integrins Mediate Invasive Activity of Mouse Mammary Carcinoma Cells through Regulation of Stromelysin-1 Expression

1999 ◽  
Vol 10 (2) ◽  
pp. 271-282 ◽  
Author(s):  
André Lochter ◽  
Marc Navre ◽  
Zena Werb ◽  
Mina J. Bissell
Keyword(s):  
Cell Migration ◽  
Cell Adhesion ◽  
Basement Membrane ◽  
Tumor Cell ◽  
Cell Invasion ◽  
Mammary Carcinoma ◽  
Carcinoma Cells ◽  
Tumor Cell Invasion ◽  
Mouse Mammary Carcinoma ◽  
Mammary Carcinoma Cells

Tumor cell invasion relies on cell migration and extracellular matrix proteolysis. We investigated the contribution of different integrins to the invasive activity of mouse mammary carcinoma cells. Antibodies against integrin subunits α6 and β1, but not against α1 and α2, inhibited cell locomotion on a reconstituted basement membrane in two-dimensional cell migration assays, whereas antibodies against β1, but not against α6 or α2, interfered with cell adhesion to basement membrane constituents. Blocking antibodies against α1 integrins impaired only cell adhesion to type IV collagen. Antibodies against α1, α2, α6, and β1, but not α5, integrin subunits reduced invasion of a reconstituted basement membrane. Integrins α1 and α2, which contributed only marginally to motility and adhesion, regulated proteinase production. Antibodies against α1 and α2, but not α6 and β1, integrin subunits inhibited both transcription and protein expression of the matrix metalloproteinase stromelysin-1. Inhibition of tumor cell invasion by antibodies against α1 and α2 was reversed by addition of recombinant stromelysin-1. In contrast, stromelysin-1 could not rescue invasion inhibited by anti-α6 antibodies. Our data indicate that α1 and α2 integrins confer invasive behavior by regulating stromelysin-1 expression, whereas α6 integrins regulate cell motility. These results provide new insights into the specific functions of integrins during tumor cell invasion.

scholarly journals CD44/chondroitin sulfate proteoglycan and alpha 2 beta 1 integrin mediate human melanoma cell migration on type IV collagen and invasion of basement membranes.

1996 ◽  
Vol 7 (3) ◽  
pp. 383-396 ◽  
Author(s):  
J R Knutson ◽  
J Iida ◽  
G B Fields ◽  
J B McCarthy
Keyword(s):  
Cell Migration ◽  
Cell Adhesion ◽  
Cell Surface ◽  
Tumor Cell ◽  
Melanoma Cell ◽  
Cell Invasion ◽  
Type Iv Collagen ◽  
Human Melanoma ◽  
Type Iv ◽  
Beta 1 Integrin

Tumor cell invasion of basement membranes (BM) represents one of the critical steps in the metastatic process. Tumor cell recognition of individual BM matrix components may involve individual cell adhesion receptors, such as integrins or cell surface proteoglycans, or may involve a coordinate action of both types of receptors. In this study, we have focused on the identification of a cell surface CD44/chondroitin sulfate proteoglycan (CSPG) and alpha 2 beta 1 integrin on human melanoma cells that are both directly involved in the in vitro invasion of reconstituted BM via a type IV collagen-dependent mechanism. Interfering with cell surface expression of human melanoma CSPG with either p-nitro-phenyl-beta-D-xylopyranoside treatment or anti-CD44 monoclonal antibody (mAb) preincubation (mAb) preincubation inhibits melanoma cell invasion through reconstituted BM. These treatments also strongly inhibit melanoma cell migration on type IV collagen, however, they are ineffective at inhibiting cell adhesion to type IV collagen. Purified melanoma cell surface CD44/CSPG, or purified chondroitin sulfate, bind to type IV collagen affinity columns, consistent with a role for CD44/CSPG-type IV collagen interactions in mediating tumor cell invasion. In contrast, melanoma cell migration on laminin (LM) does not involve CD44/CSPG, nor does CD44/CSPG bind to LM, suggesting that CD44/CSPG-type IV collagen interactions are specific in nature. Additionally, anti-alpha 2 and anti-beta 1 integrin mAbs are capable of blocking melanoma cell invasion of reconstituted BM. Both of these anti-integrin mAbs inhibit melanoma cell adhesion and migration on type IV collagen, whereas only anti-beta 1 mAb inhibits cell adhesion to LM. Collectively, these results indicate that melanoma cell adhesion to type IV collagen is an important consideration in invasion of reconstituted BM in vitro, and suggest that CD44/CSPG and alpha 2 beta 1 integrin may collaborate to promote human melanoma cell adhesion, migration, and invasion in vivo.

Platelet and Shear Rate Promote Tumor Cell Adhesion to Human Endothelial Extracellular Matrix - Absence of a Role for Platelet Cyclooxygenase

1989 ◽  
Vol 61 (03) ◽  
pp. 485-489 ◽  
Author(s):  
Eva Bastida ◽  
Lourdes Almirall ◽  
Antonio Ordinas
Keyword(s):  
Cell Adhesion ◽  
Shear Rate ◽  
Tumor Cell ◽  
Umbilical Vein ◽  
Blood Platelets ◽  
Flow Conditions ◽  
Tumor Cell Adhesion ◽  
Rate Dependent ◽  
Static Conditions

SummaryBlood platelets are thought to be involved in certain aspects of malignant dissemination. To study the role of platelets in tumor cell adherence to vascular endothelium we performed studies under static and flow conditions, measuring tumor cell adhesion in the absence or presence of platelets. We used highly metastatic human adenocarcinoma cells of the lung, cultured human umbilical vein endothelial cells (ECs) and extracellular matrices (ECM) prepared from confluent EC monolayers. Our results indicated that under static conditions platelets do not significantly increase tumor cell adhesion to either intact ECs or to exposed ECM. Conversely, the studies performed under flow conditions using the flat chamber perfusion system indicated that the presence of 2 × 105 pl/μl in the perfusate significantly increased the number of tumor cells adhered to ECM, and that this effect was shear rate dependent. The maximal values of tumor cell adhesion were obtained, in presence of platelets, at a shear rate of 1,300 sec-1. Furthermore, our results with ASA-treated platelets suggest that the role of platelets in enhancing tumor cell adhesion to ECM is independent of the activation of the platelet cyclooxygenase pathway.

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