Oncogenic Properties of Candidate Oncogenes in Chromosome Region 17p11.2p12 in Human Osteosarcoma

2016 ◽  
Vol 150 (1) ◽  
pp. 52-59 ◽  
Author(s):  
Joeri Both ◽  
Thijs Wu ◽  
Anneloor L.M.A. ten Asbroek ◽  
Frank Baas ◽  
Theo J.M. Hulsebos
Keyword(s):  
Cell Lines ◽  
Chromosome Region ◽  
Migration And Invasion ◽  
Osteosarcoma Cell ◽  
High Grade ◽  
Primary Tumors ◽  
Genomic Changes ◽  
Human Osteosarcoma ◽  
Tumors Of Bone

Osteosarcomas are primary tumors of bone that most often develop in adolescents. They are characterized by complex genomic changes including amplifications, deletions, and translocations. The chromosome region 17p11.2p12 is frequently amplified in human high grade osteosarcomas (25% of cases), suggesting the presence of one or more oncogenes. In previous studies, we identified 9 candidate oncogenes in this region (GID4, ARGHAP44, LRRC75A-AS1, TOP3A, COPS3, SHMT1, PRPSAP2, PMP22, and RASD1). The aim of the present study was to determine their oncogenic properties. Therefore, we generated osteosarcoma cell lines overexpressing these genes, except for LRRC75A-AS1 and PRPSAP2, and subjected these to functional oncogenic assays. We found that TOP3A, SHMT1, and RASD1 overexpression provided increased proliferation and that ARGHAP44, COPS3, and PMP22 overexpression had a stimulatory effect on migration and invasion of the cells. COPS3 and PMP22 overexpression additionally improved the ability of the cells to form new colonies. No oncogenic effect could be demonstrated for GID4 overexpression. We conclude that the concerted amplification-mediated overexpression of these genes in 17p11.2p12 may contribute to the oncogenic process in malignant osteosarcoma.

scholarly journals MiR-125b Functions as a Tumor Suppressor and Enhances Chemosensitivity to Cisplatin in Osteosarcoma

2016 ◽  
Vol 15 (6) ◽  
pp. NP105-NP112 ◽  
Author(s):  
Fei Wang ◽  
Dapeng Yu ◽  
Zhen Liu ◽  
Ruijie Wang ◽  
Yan Xu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Suppressor ◽  
Cell Lines ◽  
Noncoding Rna ◽  
Migration And Invasion ◽  
Osteosarcoma Cell ◽  
Human Osteosarcoma ◽  
Translational Level

MicroRNAs are highly conserved noncoding RNA that negatively modulate protein expression at a posttranscriptional and/or translational level and are deeply involved in the pathogenesis of several types of cancers. To date, the potential microRNAs regulating the growth and progression of osteosarcoma are not fully identified yet. Previous reports have shown differentially expressed miR-125b in osteosarcoma. However, the role of miR-125b in human osteosarcoma has not been totally illuminated. In this study, we have shown that miR-125b was downregulated in human osteosarcoma tissues compared to the adjacent tissues and effects as a tumor suppressor in vitro. We found that stable overexpression of miR-125b in osteosarcoma cell lines U2OS and MG-63 inhibited cell proliferation, migration, and invasion. Our data also verified that Bcl-2 is the target of miR-125b. Meanwhile, we showed that Bcl-2 was inversely correlated with miR-125b in osteosarcoma tissues. More importantly, we proved that miR-125b increased the chemosensitivity of osteosarcoma cell lines to cisplatin by targeting Bcl-2. In conclusion, our data demonstrate that miR-125b is a tumor suppressor and support its potential application for the treatment of osteosarcoma in the future.

scholarly journals Possible contribution of aminopeptidase N (APN/CD13) to migration and invasion of human osteosarcoma cell lines

2014 ◽  
Vol 45 (6) ◽  
pp. 2475-2485 ◽  
Author(s):  
WENQING LIANG ◽  
BO GAO ◽  
GUOJIAN XU ◽  
DONG WENG ◽  
MINGHUA XIE ◽  
...  
Keyword(s):  
Cell Lines ◽  
Aminopeptidase N ◽  
Migration And Invasion ◽  
Osteosarcoma Cell ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cell

scholarly journals Anti-Metastatic and Anti-Angiogenic Effects of Curcumin Analog DK1 on Human Osteosarcoma Cells In Vitro

2021 ◽  
Vol 14 (6) ◽  
pp. 532
Author(s):  
Muhammad Nazirul Mubin Aziz ◽  
Nurul Fattin Che Rahim ◽  
Yazmin Hussin ◽  
Swee Keong Yeap ◽  
Mas Jaffri Masarudin ◽  
...  
Keyword(s):  
Cell Lines ◽  
Safety Profile ◽  
Quantitative Polymerase Chain Reaction ◽  
Tube Formation ◽  
Osteosarcoma Cell ◽  
Curcumin Analog ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cells ◽  
Human Osteosarcoma Cell

Osteosarcoma (OS) is a life-threatening malignant bone tumor associated with poor prognosis among children. The survival rate of the patient is still arguably low even with intensive treatment provided, plus with the inherent side effects from the chemotherapy, which gives more unfavorable outcomes. Hence, the search for potent anti-osteosarcoma agent with promising safety profile is still on going. Natural occurring substance like curcumin has gained a lot of attention due to its splendid safety profile as well as it pharmacological advantages such as anti-metastasis and anti-angiogenesis. However, natural curcumin was widely known for its poor cellular uptake, which undermines all potential that it possesses. This prompted the development of synthetically synthesized curcuminoid analog, known as (Z)-3-hydroxy-1-(2-hydroxyphenyl)-3-phenylprop-2- en-1-one (DK1). In this present study, in vitro scratch assay, transwell migration/invasion assay, HUVEC tube formation assay, and ex vivo rat aortic ring assays were performed in order to investigate the anti-metastatic and anti-angiogenic potential of DK1. For further comprehension of DK1 mechanism on human osteosarcoma cell lines, microarray gene expression analysis, quantitative polymerase chain reaction (qPCR), and proteome profiler were adopted, providing valuable forecast from the expression of important genes and proteins related to metastasis and angiogenesis. Based on the data gathered from the bioassays, DK1 was able to inhibit the metastasis and angiogenesis of human osteosarcoma cell lines by significantly reducing the cell motility, number of migrated and invaded cells as well as the tube formation and micro-vessels sprouting. Additionally, DK1 also has significantly regulated several cancer pathways involved in OS proliferation, metastasis, and angiogenesis such as PI3K/Akt and NF-κB in both U-2 OS and MG-63. Regulation of PI3K/Akt caused up-regulation of genes related to metastasis inhibition, namely, PTEN, FOXO, PLK3, and GADD45A. Meanwhile, NF-κB pathway was regulated by mitigating the expression of NF-κB activator such as IKBKB and IKBKE in MG-63, whilst up-regulating the expression of NF-κB inhibitors such as NFKBIA and NFKBIE in U-2 OS. Finally, DK1 also has successfully hindered the metastatic and angiogenic capability of OS cell lines by down-regulating the expression of pro-metastatic genes and proteins like MMP3, COL11A1, FGF1, Endoglin, uPA, and IGFBP2 in U-2 OS. Whilst for MG-63, the significantly down-regulated oncogenes were Serpin E1, AKT2, VEGF, uPA, PD-ECGF, and Endoglin. These results suggest that curcumin analog DK1 may serve as a potential new anti-osteosarcoma agent due to its anti-metastatic and anti-angiogenic attributes.

scholarly journals Loss of 5′-Methylthioadenosine Phosphorylase (MTAP) is Frequent in High-Grade Gliomas; Nevertheless, it is Not Associated with Higher Tumor Aggressiveness

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 492 ◽  
Author(s):  
Weder Pereira de Menezes ◽  
Viviane Aline Oliveira Silva ◽  
Izabela Natália Faria Gomes ◽  
Marcela Nunes Rosa ◽  
Maria Luisa Corcoll Spina ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
In Silico ◽  
Glioma Cell ◽  
Clinicopathological Features ◽  
Migration And Invasion ◽  
High Grade ◽  
Methylthioadenosine Phosphorylase ◽  
Frequent Event ◽  
High Grade Gliomas

The 5’-methylthioadenosine phosphorylase (MTAP) gene is located in the chromosomal region 9p21. MTAP deletion is a frequent event in a wide variety of human cancers; however, its biological role in tumorigenesis remains unclear. The purpose of this study was to characterize the MTAP expression profile in a series of gliomas and to associate it with patients’ clinicopathological features. Moreover, we sought to evaluate, through glioma gene-edited cell lines, the biological impact of MTAP in gliomas. MTAP expression was evaluated in 507 glioma patients by immunohistochemistry (IHC), and the expression levels were associated with patients’ clinicopathological features. Furthermore, an in silico study was undertaken using genomic databases totalizing 350 samples. In glioma cell lines, MTAP was edited, and following MTAP overexpression and knockout (KO), a transcriptome analysis was performed by NanoString Pan-Cancer Pathways panel. Moreover, MTAP’s role in glioma cell proliferation, migration, and invasion was evaluated. Homozygous deletion of 9p21 locus was associated with a reduction of MTAP mRNA expression in the TCGA (The Cancer Genome Atlas) - glioblastoma dataset (p < 0.01). In addition, the loss of MTAP expression was markedly high in high-grade gliomas (46.6% of cases) determined by IHC and Western blotting (40% of evaluated cell lines). Reduced MTAP expression was associated with a better prognostic in the adult glioblastoma dataset (p < 0.001). Nine genes associated with five pathways were differentially expressed in MTAP-knockout (KO) cells, with six upregulated and three downregulated in MTAP. Analysis of cell proliferation, migration, and invasion did not show any significant differences between MTAP gene-edited and control cells. Our results integrating data from patients as well as in silico and in vitro models provide evidence towards the lack of strong biological importance of MTAP in gliomas. Despite the frequent loss of MTAP, it seems not to have a clinical impact in survival and does not act as a canonic tumor suppressor gene in gliomas.

scholarly journals Establishment and characterization of human osteosarcoma cell lines with different pulmonary metastatic potentials

2009 ◽  
Vol 61 (1-2) ◽  
pp. 37-44 ◽  
Author(s):  
Xiang Chen ◽  
Tong-Tao Yang ◽  
Wei Wang ◽  
Hong-Hui Sun ◽  
Bao-An Ma ◽  
...  
Keyword(s):  
Cell Lines ◽  
Osteosarcoma Cell ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cell

scholarly journals Rhotekin 2 silencing inhibits proliferation and induces apoptosis in human osteosarcoma cells

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Xiong Wang ◽  
Lei Zhang ◽  
Wenji Wang ◽  
Yuchen Wang ◽  
Ye Chen ◽  
...  
Keyword(s):  
Cell Lines ◽  
Phase Cell ◽  
Osteosarcoma Cell ◽  
Cyclin Dependent Kinase ◽  
Potential Therapeutic Target ◽  
Human Osteosarcoma ◽  
Cycle Arrest ◽  
Human Osteosarcoma Cells ◽  
Human Osteosarcoma Cell ◽  
Induced Apoptosis

Human osteosarcoma is the most frequent primary malignant of bone, and often occurs in adolescents. However, molecular mechanism of this disease remains unclear. In the present study, we found that the level of Rhotekin 2 (RTKN2) was up-regulated in osteosarcoma tissues and cell lines. In addition, silencing of RTKN2 of human osteosarcoma cell lines U2OS, inhibited proliferation, and induced G1 phase cell cycle arrest via reducing the level of the cyclin-dependent kinase 2 (CDK2). Furthermore, RTKN2 knockdown in the U2OS cells induced apoptosis by increasing the level of Bax and decreasing the level of Bcl2. These results suggested that RTKN2 is involved in the progression of human osteosarcoma, and may be a potential therapeutic target.

scholarly journals Establishment and characterization ofin vivoorthotopic bioluminescent xenograft models from human osteosarcoma cell lines in Swiss nude and NSG mice

2018 ◽  
Vol 7 (3) ◽  
pp. 665-676 ◽  
Author(s):  
Maria Eugenia Marques da Costa ◽  
Estelle Daudigeos-Dubus ◽  
Anne Gomez-Brouchet ◽  
Olivia Bawa ◽  
Valerie Rouffiac ◽  
...  
Keyword(s):  
Cell Lines ◽  
Osteosarcoma Cell ◽  
Human Osteosarcoma ◽  
Nsg Mice ◽  
Human Osteosarcoma Cell ◽  
Xenograft Models

Alkaline phosphatase activity from human osteosarcoma cell line SaOS-2: an isoenzyme standard for quantifying skeletal alkaline phosphatase activity in serum.

1989 ◽  
Vol 35 (2) ◽  
pp. 223-229 ◽  
Author(s):  
J R Farley ◽  
E Kyeyune-Nyombi ◽  
N M Tarbaux ◽  
S L Hall ◽  
D D Strong
Keyword(s):  
Alkaline Phosphatase ◽  
Phosphatase Activity ◽  
Cell Lines ◽  
Alkaline Phosphatase Activity ◽  
Osteosarcoma Cell ◽  
Kinetic Assay ◽  
Human Osteosarcoma ◽  
Alp Activity ◽  
Human Osteosarcoma Cell ◽  
Skeletal Alkaline Phosphatase

Abstract Earlier we described a kinetic assay for quantifying skeletal alkaline phosphatase (ALP) isoenzyme activity in serum. The precision of the assay depends on including ALP standards for the skeletal, hepatic, intestinal, and placental isoenzymes. We wondered whether human osteosarcoma cells could provide an efficient alternative to human bone or Pagetic serum as a source of the skeletal ALP standard. ALP activities prepared from five human osteosarcoma cell lines were compared with a bone-derived ALP standard with respect to heat stability and sensitivity to chemical effectors. Two of the cell lines (SaOS-2 and TE-85) contained ALP activities that resembled the bone-derived standard. We selected SaOS-2 cells for additional evaluation (as a potential source of isoenzyme standard), because they contained 40-50 times more ALP activity than did the TE-85 cells. To include the SaOS-2 cell-derived ALP activity in the quantitative isoenzyme assay, we diluted the enzyme in a solution containing heat-inactivated (i.e., ALP-negative) human serum. Surprisingly, this dilution caused a 60-125% increase in maximum enzyme activity. In the quantitative assay of ALP isoenzyme in serum, the SaOS-2 derived ALP was indistinguishable from the serum skeletal ALP standard, with respect to the above criteria and assay variations. Evidently ALP from SaOS-2 cells is suited as a standard for measuring skeletal ALP activity in this assay.

scholarly journals Antiproliferative Properties of Oleuropein in Human Osteosarcoma Cells

2016 ◽  
Vol 11 (4) ◽  
pp. 1934578X1601100 ◽  
Author(s):  
Jose M. Moran ◽  
Olga Leal-Hernandez ◽  
Maria L. Canal-Macías ◽  
Raul Roncero-Martin ◽  
Rafael Guerrero-Bonmatty ◽  
...  
Keyword(s):  
Cell Lines ◽  
Osteosarcoma Cell ◽  
Dependent Manner ◽  
Osteosarcoma Cells ◽  
Probit Regression ◽  
Cytotoxic Effects ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cells ◽  
Mg63 Cells ◽  
Human Osteosarcoma Cell

In this study, we evaluated the antiproliferative activity on two human osteosarcoma cell lines (MG-63 and Saos2) of oleuropein, an olive oil compound traditionally found in the Mediterranean diet. Oleuropein exhibited obvious cytotoxic effects on human osteosarcoma cells in a concentration- and time-dependent manner. Statistical analysis of IC50 by the Probit regression method suggested that oleuropein had similar toxic effects on both cell lines tested (IC50 range from 247.4–475.0 μM for MG63 cells and from 798.7–359.9 μM for Saos2 cells).

Betulin inhibits mTOR and induces autophagy to promote apoptosis in human osteosarcoma cell lines

2020 ◽  
Vol 35 (8) ◽  
pp. 879-887 ◽  
Author(s):  
Yung‐Chi Lin ◽  
Hsuan‐Ying Chen ◽  
Cheng‐Pu Hsieh ◽  
Yi‐Fu Huang ◽  
Ing‐Lin Chang
Keyword(s):  
Cell Lines ◽  
Osteosarcoma Cell ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cell
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