scholarly journals Role of Cell Surface Metalloprotease Mt1-Mmp in Epithelial Cell Migration over Laminin-5

2000 ◽  
Vol 148 (3) ◽  
pp. 615-624 ◽  
Author(s):  
Naohiko Koshikawa ◽  
Gianluigi Giannelli ◽  
Vincenzo Cirulli ◽  
Kaoru Miyazaki ◽  
Vito Quaranta
Keyword(s):  
Cell Lines ◽  
Cancer Metastasis ◽  
Gelatin Zymography ◽  
Basement Membranes ◽  
Cancer Tissue ◽  
Laminin 5 ◽  
Cell Adhesion And Migration ◽  
And Migration ◽  
Tissue Specimens ◽  
Epithelial Basement

Laminin-5 (Ln-5) is an extracellular matrix substrate for cell adhesion and migration, which is found in many epithelial basement membranes. Mechanisms eliciting migration on Ln-5 need to be elucidated because of their relevance to tissue remodeling and cancer metastasis. We showed that exogenous addition of activated matrix metalloprotease (MMP) 2 stimulates migration onto Ln-5 in breast epithelial cells via cleavage of the γ2 subunit. To investigate the biological scope of this proteolytic mechanism, we tested a panel of cells, including colon and breast carcinomas, hepatomas, and immortalized hepatocytes, selected because they migrated or scattered constitutively in the presence of Ln-5. We found that constitutive migration was inhibited by BB94 or TIMPs, known inhibitors of MMPs. Limited profiling by gelatin zymography and Western blotting indicated that the ability to constitutively migrate on Ln-5 correlated with expression of plasma membrane bound MT1-MMP metalloprotease, rather than secretion of MMP2, since MMP2 was not produced by three cell lines (one breast and two colon carcinomas) that constitutively migrated on Ln-5. Moreover, migration on Ln-5 was reduced by MT1-MMP antisense oligonucleotides both in MMP2+ and MMP2− cell lines. MT1-MMP directly cleaved Ln-5, with a pattern similar to that of MMP2. The hemopexin-like domain of MMP2, which interferes with MMP2 activation, reduced Ln-5 migration in MT1-MMP+, MMP2+ cells, but not in MT1-MMP+, MMP2− cells. These results suggest a model whereby expression of MT1-MMP is the primary trigger for migration over Ln-5, whereas MMP2, which is activated by MT1-MMP, may play an ancillary role, perhaps by amplifying the MT1-MMP effects. Codistribution of MT1-MMP with Ln-5 in colon and breast cancer tissue specimens suggested a role for this mechanism in invasion. Thus, Ln-5 cleavage by MMPs may be a widespread mechanism that triggers migration in cells contacting epithelial basement membranes.

The EphA3 receptor is expressed in a subset of rhabdomyosarcoma cell lines and suppresses cell adhesion and migration

2008 ◽  
Vol 105 (5) ◽  
pp. 1250-1259 ◽  
Author(s):  
Noretta Clifford ◽  
Loraine M. Smith ◽  
James Powell ◽  
Stefan Gattenlöhner ◽  
Alexander Marx ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Cell Lines ◽  
Rhabdomyosarcoma Cell ◽  
Cell Adhesion And Migration ◽  
And Migration

scholarly journals Knockdown of lncRNA FEZF1-AS1 Inhibits metastasis of Osteosarcoma Cells by miR-4456/GALNT10

2020 ◽  
Author(s):  
Zhenxing Si ◽  
Shifeng Zhou ◽  
Zilong Shen ◽  
Feiyu Luan ◽  
jinglong yan
Keyword(s):  
Cell Lines ◽  
Antisense Rna ◽  
Malignant Tumors ◽  
Luciferase Assay ◽  
Cell Infiltration ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Therapeutic Development ◽  
And Migration ◽  
Tissue Specimens

Abstract Background: Osteosarcoma (OS) is among the malignant tumors with high mortality and low survival, especially in children and adolescents. Research shows that LncRNA FEZ family zinc finger 1 antisense RNA 1 (FEZF1-AS1) enhances osteosarcoma progression. Nevertheless, the function and mechanism of FEZF1-AS1 in metastasis of OS remains unclear.Methods: We used qRT-PCR to assay for the expression of FEZF1-AS1, miR-4456, and GALNT10 in OS tissue specimens and cell lines. We also investigated the progression of OS through metastasis using the wound healing and Transwell assays. Moreover, we used the dual-luciferase reporter test, RIP assays, and western blot to validate whether FEZF1-AS1 serves as a competing endogenous RNA (ceRNA), modulating the expression of GALNT10 through sponging miR-4456 in OS.Results: FEZF1-AS1 was up modulated in OS tissues. Silencing FEZF1-AS1 repressed OS cell migration and invasion. microRNA-4456 (miR-4456) was involved in FEZF1-AS1-induced migration and invasion. miR-4456 was down modulated in OS tissue specimens and cell lines. Functionally, the up modulation of miR-4456 reversed the facilitative influence of FEZF1-AS1 on OS cell infiltration and migration. Mechanically, FEZF1-AS1 interacted with miR-4456 in a reciprocal suppressed manner. Moreover, miR-4456 targets GALNT10 via the Luciferase assay. Besides, the up modulation of GALNT10 reversed the migration and invasion inhibited by FEZF1-AS1 knockdown. Silencing of FEZF1-AS1 inhibits OS cell infiltration and migration through miR-4456 /GALNT10 sponging.Conclusion: Herein, we demonstrated that FEZF1-AS1 is a prospective bio signature of metastasis in OS patients. Mechanistically, we showed that the FEZF1-AS1/miR-4456/GALNT10 axis is a target for novel therapeutic development for OS.

scholarly journals Long Noncoding RNA MALAT1 Interacts with miR-124-3p to Modulate Osteosarcoma Progression by Targeting SphK1

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Bin Liu ◽  
Xinli Zhan ◽  
Chong Liu
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Noncoding Rna ◽  
Underlying Mechanism ◽  
Luciferase Reporter ◽  
Cell Proliferation And Migration ◽  
Lncrna Malat1 ◽  
And Migration ◽  
Tissue Specimens ◽  
Proliferation And Migration

Introduction. Long noncoding RNAs (lncRNAs) have been implicated in a variety of biological functions, including tumor proliferation, apoptosis, progression, and metastasis. lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is overexpressed in various cancers, as well as osteosarcoma (OS); however, its underlying mechanism in OS is poorly understood. This investigation aims to elucidate the mechanisms of MALAT1 in OS proliferation and migration and to provide theoretical grounding for further targeted therapy in OS. Methods. In the present study, we applied qRT-PCR to assess the MALAT1 expression in OS tissues and cell lines. The effects of MALAT1 and miR-124-3p on OS cell proliferation and migration were studied by CCK-8 and scratch assays. Cell cycle and apoptosis were tested using a flow cytometer. The competing relationship between MALAT1 and miR-124-3p was confirmed by dual-luciferase reporter assay. Results. MALAT1 was overexpressed in OS cell lines and tissue specimens, and knockdown of MALAT1 significantly inhibited cell proliferation and migration and increased cell apoptosis and the percentage of G0/G1 phase. Furthermore, MALAT1 could directly bind to miR-124-3p and inhibit miR-124-3p expression. Moreover, MALAT1 overexpression significantly relieved the inhibition on OS cell proliferation mediated by miR-124-3p overexpression, which involved the derepression of sphingosine kinase 1 (SphK1). Conclusions. We propose that lncRNA MALAT1 interacts with miR-124-3p to modulate OS progression by targeting SphK1. Hence, we identified a novel MALAT1/miR-124-3p/SphK1 signaling pathway in the regulation of OS biological behaviors.

scholarly journals Metabolite secretions of Lactobacillus plantarum YYC-3 may inhibit colon cancer cell metastasis by suppressing the VEGF-MMP2/9 signaling pathway

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Yuan-Chun Yue ◽  
Bao-Yu Yang ◽  
Jing Lu ◽  
Shu-Wen Zhang ◽  
Liu Liu ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Signaling Pathway ◽  
Cancer Metastasis ◽  
Gelatin Zymography ◽  
Inhibitory Effect ◽  
Invasion And Migration ◽  
Cell Metastasis ◽  
Gene And Protein Expression ◽  
Q Exactive ◽  
And Migration

Abstract Background Colorectal cancer (CRC) is a major clinical challenge, and the gut microbiome plays important roles in the occurrence and metastasis of CRC. Lactobacillus and their metabolites are thought to be able to suppress the growth of CRC cells. However, the antimetastatic mechanism of Lactobacillus or their metabolites toward CRC cells is not clear. Therefore, the aim of this study was to assess the inhibitory mechanism of cell-free supernatants (CFSs) of L. rhamnosus GG, L. casei M3, and L. plantarum YYC-3 on metastasis of CRC cells. Results YYC-3 CFS showed the highest inhibitory effect on CRC cell growth, invasion and migration, and inhibited MMP2, MMP9, and VEGFA gene and protein expression, and protein secretion. Furthermore, it suppressed the activities of MMPs by gelatin zymography. Moreover, the effective compounds in these CFSs were analyzed by Q Exactive Focus liquid chromatography–mass spectrometry. Conclusions Our results showed that metabolite secretions of YYC-3 may inhibited cell metastasis by downregulating the VEGF/MMPs signaling pathway. These data suggest that treatment of CRC cells with metabolites from L. plantarum YYC-3 may reduce colon cancer metastasis.

scholarly journals The evaluation of Melatonin and EGF interaction on breast cancer metastasis

2021 ◽  
Author(s):  
Maryam Akbarzadeh
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Metastasis ◽  
Migration And Invasion ◽  
Breast Cancer Cell Lines ◽  
Breast Cancer Patients ◽  
Mcf7 Cells ◽  
And Migration

Abstract Background Breast cancer is currently one of the most common types of cancer in women, and metastasis is the first cause of death in breast cancer patients. The epidermal growth factor (EGF) increases the invasion, growth, and migration of cancer cells. In the present study, melatonin, as a natural hormone, in EGF-induced tumor metastasis, was investigated. Methods First, MDA-MB-231 and MCF7 cells were cultured, and then the effects of melatonin on cell viability were determined by MTT assay. Transwell invasion assay was employed to identify the invasiveness of these breast cancer cell lines. Real-time RT-PCR then investigated the expression of MMP9 and MMP2. Cell proliferation was also determined under EGF and melatonin treatment using Ki67 assessment by flow cytometry. Results The rate of invasion and migration of EGF-treated cells increased in both groups, in which melatonin caused increased invasion by EGF in MCF7 cells. MMP9 and MMP2 expression increased significantly in both cell lines under EGF treatment, and melatonin increased these genes' expression in both cell lines (p <0.05). EGF increased the MMP9 and MMP2 gene expression, and melatonin increases EGF-induced expression(p <0.05). The EGF reduced the expression of the Ki67 protein in the MCF7 cell line, which was negatively affected by Melatonin and EGF. In contrast, along with Melatonin, EGF did not affect the proliferation of the MDA-MB-231 cell line. Conclusions Our results show that melatonin, as a natural compound, can increase the effects of EGF in the proliferation, migration, and invasion of cancer cells at low dosages.

scholarly journals Human Organoid and Supporting Technologies for Cancer and Toxicological Research

2021 ◽  
Vol 12 ◽  
Author(s):  
Keisuke Sekine
Keyword(s):  
Cell Lines ◽  
Cancer Progression ◽  
Cancer Metastasis ◽  
Human Cancer ◽  
Cancer Tissue ◽  
Carcinogenic Activity ◽  
Cultured Cell ◽  
Human Cancer Cells ◽  
Cell Culture Systems ◽  
Different Genetic Background

Recent progress in the field of organoid-based cell culture systems has enabled the use of patient-derived cells in conditions that resemble those in cancer tissue, which are better than two-dimensional (2D) cultured cell lines. In particular, organoids allow human cancer cells to be handled in conditions that resemble those in cancer tissue, resulting in more efficient establishment of cells compared with 2D cultured cell lines, thus enabling the use of multiple patient-derived cells with cells from different genetic background, in keeping with the heterogeneity of the cells. One of the most valuable points of using organoids is that human cells from either healthy or cancerous tissue can be used. Using genome editing technology such as clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein, organoid genomes can be modified to, for example, cancer-prone genomes. The normal, cancer, or genome-modified organoids can be used to evaluate whether chemicals have genotoxic or non-genotoxic carcinogenic activity by evaluating the cancer incidence, cancer progression, and cancer metastasis. In this review, the organoid technology and the accompanying technologies were summarized and the advantages of organoid-based toxicology and its application to pancreatic cancer study were discussed.

scholarly journals Structural Requirement of Carboxyl-terminal Globular Domains of Laminin α3 Chain for Promotion of Rapid Cell Adhesion and Migration by Laminin-5

2000 ◽  
Vol 275 (29) ◽  
pp. 22495-22502 ◽  
Author(s):  
Tomomi Hirosaki ◽  
Hiroto Mizushima ◽  
Yoshiaki Tsubota ◽  
Kayano Moriyama ◽  
Kaoru Miyazaki
Keyword(s):  
Cell Adhesion ◽  
Structural Requirement ◽  
Laminin 5 ◽  
Cell Adhesion And Migration ◽  
Carboxyl Terminal ◽  
And Migration

Glioblastoma invasion and NMDA receptors: A novel prospect

2019 ◽  
Vol 106 (3) ◽  
pp. 250-260 ◽  
Author(s):  
DN Nandakumar ◽  
P Ramaswamy ◽  
C Prasad ◽  
D Srinivas ◽  
K Goswami
Keyword(s):  
Glutamate Receptors ◽  
Cell Lines ◽  
Intracellular Signaling ◽  
Transcript Level ◽  
Glioblastoma Cells ◽  
Invasion And Migration ◽  
Matrigel Invasion ◽  
Nmdar Activation ◽  
And Migration

Purpose Glioblastoma cells create glutamate-rich tumor microenvironment, which initiates activation of ion channels and modulates downstream intracellular signaling. N-methyl-D-aspartate receptors (NMDARs; a type of glutamate receptors) have a high affinity for glutamate. The role of NMDAR activation on invasion of glioblastoma cells and the crosstalk with α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) is yet to be explored. Main methods LN18, U251MG, and patient-derived glioblastoma cells were stimulated with NMDA to activate NMDAR glutamate receptors. The role of NMDAR activation on invasion and migration and its crosstalk with AMPAR were evaluated. Invasion and migration of glioblastoma cells were investigated by in vitro trans-well Matrigel invasion and trans-well migration assays, respectively. Expression of NMDARs and AMPARs at transcript level was evaluated by quantitative real-time polymerase chain reaction. Results We determined that NMDA stimulation leads to enhanced invasion in LN18, U251MG, and patient-derived glioblastoma cells, whereas inhibition of NMDAR using MK-801, a non-competitive antagonist of the NMDAR, significantly decreased the invasive capacity. Concordant with these findings, migration was significantly augmented by NMDAR in both cell lines. Furthermore, NMDA stimulation upregulated the expression of GluN2 and GluA1 subunits at the transcript level. Conclusions This study demonstrated the previously unexplored role of NMDAR in invasion of glioblastoma cells. Furthermore, the expression of the GluN2 subunit of NMDAR and the differential overexpression of the GluA1 subunit of AMPAR in both cell lines provide a plausible rationale of crosstalk between these calcium-permeable subunits in the glutamate-rich microenvironment of glioblastoma.

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