scholarly journals CCL4 Stimulates Cell Migration in Human Osteosarcoma via the mir-3927-3p/Integrin αvβ3 Axis

2021 ◽  
Vol 22 (23) ◽  
pp. 12737
Author(s):  
Hsiao-Chi Tsai ◽  
Yan-You Lai ◽  
Hsuan-Chih Hsu ◽  
Yi-Chin Fong ◽  
Ming-Yu Lien ◽  
...  
Keyword(s):  
Cell Migration ◽  
Hypoxia Inducible Factor ◽  
Bone Cancer ◽  
Integrin Αvβ3 ◽  
Gene Expression Omnibus ◽  
Osteosarcoma Cell ◽  
Hypoxia Inducible Factor 1 ◽  
Human Osteosarcoma ◽  
Metastatic Osteosarcoma ◽  
Geo Dataset

Osteosarcoma is the most common type of primary malignant bone cancer, and it is associated with high rates of pulmonary metastasis. Integrin αvβ3 is critical for osteosarcoma cell migratory and invasive abilities. Chemokine (C-C motif) ligand 4 (CCL4) has diverse effects on different cancer cells through its interaction with its specific receptor, C-C chemokine receptor type 5 (CCR5). Analysis of mRNA expression in human osteosarcoma tissue identified upregulated levels of CCL4, integrin αv and β3 expression. Similarly, an analysis of records from the Gene Expression Omnibus (GEO) dataset showed that CCL4 was upregulated in human osteosarcoma tissue. Importantly, the expression of both CCL4 and integrin αvβ3 correlated positively with osteosarcoma clinical stages and lung metastasis. Analysis of osteosarcoma cell lines identified that CCL4 promotes integrin αvβ3 expression and cell migration by activating the focal adhesion kinase (FAK), protein kinase B (AKT), and hypoxia inducible factor 1 subunit alpha (HIF-1α) signaling pathways, which can downregulate microRNA-3927-3p expression. Pharmacological inhibition of CCR5 by maraviroc (MVC) prevented increases in integrin αvβ3 expression and cell migration. This study is the first to implicate CCL4 as a potential target in the treatment of metastatic osteosarcoma.

scholarly journals CXCL13/CXCR5 Interaction Facilitates VCAM-1-Dependent Migration in Human Osteosarcoma

2020 ◽  
Vol 21 (17) ◽  
pp. 6095 ◽  
Author(s):  
Ju-Fang Liu ◽  
Chiang-Wen Lee ◽  
Chih-Yang Lin ◽  
Chia-Chia Chao ◽  
Tsung-Ming Chang ◽  
...  
Keyword(s):  
Cell Migration ◽  
Metastatic Potential ◽  
Nuclear Factor Κb ◽  
Vital Role ◽  
Migration And Invasion ◽  
Osteosarcoma Cell ◽  
Human Osteosarcoma ◽  
Kinase C ◽  
Metastatic Osteosarcoma ◽  
Cell Adhesion Molecule 1

Osteosarcoma is the most common primary tumor of the skeletal system and is well-known to have an aggressive clinical outcome and high metastatic potential. The chemokine (C-X-C motif) ligand 13 (CXCL13) plays a vital role in the development of several cancers. However, the effect of CXCL13 in the motility of osteosarcoma cells remains uncertain. Here, we found that CXCL13 increases the migration and invasion potential of three osteosarcoma cell lines. In addition, CXCL13 expression was upregulated in migration-prone MG-63 cells. Vascular cell adhesion molecule 1 (VCAM-1) siRNA and antibody demonstrated that CXCL13 promotes migration via increasing VCAM-1 production. We also show that CXCR5 receptor controls CXCL13-mediated VCAM-1 expression and cell migration. Our study identified that CXCL13/CXCR5 axis facilitate VCAM-1 production and cell migration in human osteosarcoma via the phospholipase C beta (PLCβ), protein kinase C α (PKCα), c-Src, and nuclear factor-κB (NF-κB) signaling pathways. CXCL13 and CXCR5 appear to be a novel therapeutic target in metastatic osteosarcoma.

scholarly journals Zinc deficiency promotes endothelin secretion and endothelial cell migration through nuclear hypoxia-inducible factor-1 translocation

2019 ◽  
Vol 317 (2) ◽  
pp. C270-C276 ◽  
Author(s):  
Jessica Morand ◽  
Anne Briançon-Marjollet ◽  
Emeline Lemarie ◽  
Brigitte Gonthier ◽  
Josiane Arnaud ◽  
...  
Keyword(s):  
Wound Healing ◽  
Endothelial Cells ◽  
Cell Migration ◽  
Endothelial Cell ◽  
Zinc Deficiency ◽  
Hypoxia Inducible Factor ◽  
Endothelial Cell Migration ◽  
Hypoxia Inducible Factor 1 ◽  
Obstructive Sleep ◽  
And Function

Zinc is involved in the expression and function of various transcription factors, including the hypoxia-inducible factor-1 (HIF-1). HIF-1 and its target gene endothelin-1 (ET-1) are activated by intermittent hypoxia (IH), one of the main consequences of obstructive sleep apnea (OSA), and both play a key role in the cardiovascular consequences of IH. Because OSA and IH are associated with zinc deficiency, we investigated the effect of zinc deficiency caused by chelation on the HIF-1/ET-1 pathway and its functional consequences in endothelial cells. Primary human microvascular endothelial cells (HMVEC) were incubated with submicromolar doses of the zinc-specific membrane-permeable chelator N, N, N′, N′-tetrakis(2-pyridylmethyl)-ethylene diamine (TPEN, 0.5 µM) or ET-1 (0.01 µM) with or without bosentan, a dual ET-1-receptor antagonist. HIF-1α expression was silenced by transfection with specific siRNA. Nuclear HIF-1 content was assessed by immunofluorescence microscopy and Western blot. Migratory capacity of HMVEC was evaluated with a wound-healing scratch assay. Zinc chelation by TPEN exposure induced the translocation of the cytosolic HIF-1α subunit of HIF-1 to the nucleus as well as an HIF-1-mediated ET-1 secretion by HMVEC. Incubation with either TPEN or ET-1 increased endothelial wound-healing capacity. Both HIF-1α silencing or bosentan abolished this effect. Altogether, these results suggest that zinc deficiency upregulates ET-1 signaling through HIF-1 activation and stimulates endothelial cell migration, suggesting an important role of zinc in the vascular consequences of IH and OSA mediated by HIF-1-ET- signaling.

Inhibition of Hypoxia-inducible Factor-1 Alpha Radiosensitized MG-63 Human Osteosarcoma Cellsin Vitro

2015 ◽  
Vol 101 (5) ◽  
pp. 578-584 ◽  
Author(s):  
Zhu Jin ◽  
Yu Aixi ◽  
Qi Baiwen ◽  
Li Zonghuan ◽  
Hu Xiang
Keyword(s):  
Hypoxia Inducible Factor ◽  
Hypoxia Inducible Factor 1 ◽  
Human Osteosarcoma

CYR61 is downregulated by statins and modulates human osteosarcoma cell migration, invasion and apoptosis

Bone ◽  
2009 ◽  
Vol 44 ◽  
pp. S250
Author(s):  
O. Fromigue ◽  
Z. Hamidouche ◽  
B. Mari ◽  
P. Barbry ◽  
P.J. Marie
Keyword(s):  
Cell Migration ◽  
Osteosarcoma Cell ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cell

IGFBP-3 stimulates human osteosarcoma cell migration by upregulating VCAM-1 expression

Life Sciences ◽  
2021 ◽  
Vol 265 ◽  
pp. 118758
Author(s):  
Chia-Chia Chao ◽  
Wei-Fang Lee ◽  
Wei-Hung Yang ◽  
Chih-Yang Lin ◽  
Chien-Kuo Han ◽  
...  
Keyword(s):  
Cell Migration ◽  
Osteosarcoma Cell ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cell ◽  
Igfbp 3

scholarly journals Niclosamide Suppresses Migration and Invasion of Human Osteosarcoma Cells by Repressing TGFBI Expression via the ERK Signaling Pathway

2022 ◽  
Vol 23 (1) ◽  
pp. 484
Author(s):  
Liang-Tsai Yeh ◽  
Chiao-Wen Lin ◽  
Ko-Hsiu Lu ◽  
Yi-Hsien Hsieh ◽  
Chao-Bin Yeh ◽  
...  
Keyword(s):  
Cell Migration ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Cellular Migration ◽  
Migration And Invasion ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cells ◽  
U2os Cells

Osteosarcoma is a highly common malignant bone tumor. Its highly metastatic properties are the leading cause of mortality for cancer. Niclosamide, a salicylanilide derivative, is an oral antihelminthic drug of known anticancer potential. However, the effect of niclosamide on osteosarcoma cell migration, invasion and the mechanisms underlying have not been fully clarified. Therefore, this study investigated niclosamide’s underlying pathways and antimetastatic effects on osteosarcoma. In this study, U2OS and HOS osteosarcoma cell lines were treated with niclosamide and then subjected to assays for determining cell migration ability. The results indicated that niclosamide, at concentrations of up to 200 nM, inhibited the migration and invasion of human osteosarcoma U2OS and HOS cells and repressed the transforming growth factor beta-induced protein (TGFBI) expression of U2OS cells, without cytotoxicity. After TGFBI knockdown occurred, cellular migration and invasion behaviors of U2OS cells were significantly reduced. Moreover, niclosamide significantly decreased the phosphorylation of ERK1/2 in U2OS cells and the combination treatment of the MEK inhibitor (U0126) and niclosamide resulted in the intensive inhibition of the TGFBI expression and the migratory ability in U2OS cells. Therefore, TGFBI derived from osteosarcoma cells via the ERK pathway contributed to cellular migration and invasion and niclosamide inhibited these processes. These findings indicate that niclosamide may be a powerful preventive agent against the development and metastasis of osteosarcoma.

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