scholarly journals Genomic and Transcriptomic Characterization of Canine Osteosarcoma Cell Lines: A Valuable Resource in Translational Medicine

2021 ◽  
Vol 8 ◽  
Author(s):  
Cecilia Gola ◽  
Diana Giannuzzi ◽  
Andrea Rinaldi ◽  
Selina Iussich ◽  
Paola Modesto ◽  
...  
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Driver Mutations ◽  
Matched Pair ◽  
Osteosarcoma Cell ◽  
Driver Genes ◽  
Primary Bone Tumor ◽  
Wall Cell

Osteosarcoma (OSA) represents the most common primary bone tumor in dogs and is characterized by a highly aggressive behavior. Cell lines represent one of the most suitable and reproducible pre-clinical models, and therefore the knowledge of their molecular landscape is mandatory to investigate oncogenic mechanisms and drug response. The present study aims at determining variants, putative driver genes, and gene expression aberrations by integrating whole-exome and RNA sequencing. For this purpose, eight canine OSA cell lines and one matched pair of primary tumor and normal tissue were analyzed. Overall, cell lines revealed a mean tumor mutational burden of 9.6 mutations/Mb (range 3.9–16.8). Several known oncogenes and tumor suppressor genes, such as ALK, MYC, and MET, were prioritized as having a likely role in canine OSA. Mutations in eight genes, previously described as human OSA drivers and including TP53, PTCH1, MED12, and PI3KCA, were retrieved in our cell lines. When variants were cross-referenced with human OSA driver mutations, the E273K mutation of TP53 was identified in the Wall cell line and tumor sample. The transcriptome profiling detected two possible p53 inactivation mechanisms in the Wall cell line on the one hand, and in D17 and D22 on the other. Moreover, MET overexpression, potentially leading to MAPK/ERK pathway activation, was observed in D17 and D22 cell lines. In conclusion, our data provide the molecular characterization of a large number of canine OSA cell lines, allowing future investigations on potential therapeutic targets and associated biomarkers. Notably, the Wall cell line represents a valuable model to empower prospective in vitro studies both in human and in dogs, since the TP53 driver mutation was maintained during cell line establishment and was widely reported as a mutation hotspot in several human cancers.

scholarly journals Evaluation of Two Novel Therapeutics Against Human and Canine Osteosarcoma

2020 ◽  
Author(s):  
Heather Wilson-Robles ◽  
Tasha Miller ◽  
Chao Sima ◽  
Jianping Hua ◽  
Milana Cypert ◽  
...  
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Xenograft Model ◽  
Western Blots ◽  
Primary Bone Tumor ◽  
Murine Xenograft Model ◽  
Primary Bone ◽  
Number Of Cells

Abstract Background: Osteosarcoma (OS) is the most common primary bone tumor in both humans and canines. This tumor has an aggressive course leading to the development of metastatic lesions in most patients diagnosed with this disease. Two new novel agents, MLN9708 and SH4-54, work as a proteasome inhibitor and a STAT3 inhibitor, respectively. Targets of these drugs have been shown to be overexpressed in OS in both species. Methods: Two human and two canine OS cell lines were exposed in vitro to both drugs alone and in combination. The number of cells undergoing apoptosis, as well as the number of cells capable of invasion through a matrigel basement membrane was evaluated after exposure to the drugs. Additionally, PCR and Western blots of downstream targets were evaluated. Finally, both drugs were tested against each cell line in an in vivo murine xenograft model. Results: All four cell lines were sensitive to MLN9708, one of the human cell lines and both canine cell lines were resistant to SH4-54. MLN9708 was also better at inhibiting invasion in three of the four cell lines. In the murine xenografts MLN9708 inhibited growth and metastasis in 143B (human OS) and the combination inhibited growth in the canine OS cell line (MCKOS). Conclusions: Though SH4-54 demonstrated robust cell killing in 143B in vitro, MLN9708 demonstrated broader activity across species for the treatment of OS. Further investigation into this drug is warranted as a treatment for OS. Combination of this drug with a STAT3 inhibitor may be worthwhile in canine OS.

Characterization of Gene Expression Associated with Cyclophosphamide Resistance in Chronic Myeloid Leukemia (CML).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1532-1532
Author(s):  
Fei Bao ◽  
Mary L. Nordberg ◽  
Paula Polk ◽  
Amanda Sun ◽  
David Murray ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Cell Line ◽  
Cell Lines ◽  
Myeloid Leukemia ◽  
Resistant Cell ◽  
Parental Line ◽  
Resistant Line ◽  
Rt Pcr

Abstract Cyclophosphamide (CP) is one of the alkylating agents collectively referred to as oxazaphosphorines that are used to treat many types of cancers including myeloid leukemia. Tumor cell drug resistance is an important factor for clinical treatment failure. The mechanisms of drug resistance are multifactorial and incompletely understood. KBM-7 human CML cell line was established from blast cells from a patient in the terminal phase of CML. In the CP resistance model, the B5-180 sub-line was isolated following exposure to the in vitro active CP analog 4HC. B5-180 cells were cross-resistant to busulfan and γ-radiation. Total RNA was extracted and hybridized to Affymetrix Genechip HG-U95Av2 arrays. Each array contains 12,386 probes corresponding to approximately 9000 known human genes. Each cell line was arrayed in triplicate. Quantitative RT-PCR, Fluorescence In-Situ Hybridization (FISH) and cytogenetic analysis were performed in both cell lines. Both the KBM-7/B5 parental line and B5-180 resistant sub-line expressed high-levels of BCR-ABL transcripts by real-time RT-PCR. FISH and cytogenetic analysis revealed multiple copies of t(9;22) translocation and other additional chromosomal abnormalities such as trisomy 8, and abnormalities of chromosome 18 in both cell lines. Gene array identified 794 gene transcripts that were more than twofold (range from 2-fold to 2675-fold) over-expressed or under-expressed in the resistant line relative to the parental line. ALDH1A1 (aldehyde dehydrogenase 1 family) showed the most differential expression between sensitive and resistant cell lines, ALDH1A1 was upregulated more than 2000-fold in the resistant sub-line. ALDH-2 (aldehyde dehydrogenase 2 family mitochondrial) was also expressed substantially higher in the resistant line. This finding is consistent with the established fact that elevated ALDH activity is an important factor in the resistance of B5-180 cells to 4HC. The remaining differentially expressed genes encode proteins with a wide variety of biochemical functions, which include 44 apoptosis and 7 anti-apoptosis-related genes, 56 genes related to cell cycle and cell growth, 6 DNA repair genes, 13 genes involved in hemopoiesis and B-cell activation. We also tested the expression of the hematopietic transcription factor PU-1 and PUB, a novel PU-1 binding factor. Interestingly, the expression of PU-1 was decreased and PUB increased in the resistant clone. In conclusion, we have identified a large number of differentially expressed genes in a CP resistant cell line derived from CML blast crisis by microarray technology. Our results suggest that CP resistance is a complex phenotype that involves multiple genes and a variety of mechanisms. Real-time RT-PCR analysis and further characterization of selected genes associated with CP resistance as well as the response in vitro to tyrosine kinase inhibitors are currently under investigation.

scholarly journals Inhibition of miR-9 decreases osteosarcoma cell proliferation

2019 ◽  
Author(s):  
Wu Gang ◽  
Wei Tanjun ◽  
Huang Yong ◽  
Qin Jiajun ◽  
Zhang Yi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Clinical Stage ◽  
Metastatic Potential ◽  
In Vitro Models ◽  
Osteosarcoma Cell ◽  
Mirna Regulation ◽  
Primary Bone Tumor

Osteosarcoma (OS) is the most common primary bone tumor that affects adolescents and young adults. Disruption of microRNA (miRNA) regulation is well established in the pathophysiology of different cancers, including OS. Increased expression of miR-9 in OS positively correlates with the tumor size, clinical stage, and distant metastasis. In the present study, we used two different OS cell lines, MG-63 and Saos-2, as in vitro models. Small interfering RNA against miR-9 and miR-9 mimics were used to study the function of miR-9 in these two cell lines. We determined the effect of miR-9 inhibition on cell proliferation, cell cycle, apoptosis, and the protein expression of different genes. Our results demonstrated that miR-9 knockdown in the human OS cell lines inhibits their metastatic potential, as determined by decreased cell proliferation and cell cycle arrest, decreased invasion, and increased apoptosis. The western blot analysis showed that cadherin-1 (CDH1), matrix metalloproteinase 13 (MMP-13), forkhead box O3 (FOXO3a), Bcl-2-like protein 11 (BCL2L11), and β-catenin (CTNNB1) are involved in miR-9 signaling. Moreover, miR-9 mimics rescued the effects caused by the inhibition of miR-9 in the OS cell lines. Our findings suggest that miR-9 is important for mediating OS cell migration, invasion, metastasis, and apoptosis. Inhibition of miR-9 could be further explored as a therapeutic target to treat OS.

scholarly journals P07.01 Functional role of N-Myc in SHH type TP53 mutated MB’s metabolism

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii36-iii36
Author(s):  
K Yokogami
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Functional Role ◽  
Ex Vivo ◽  
Therapeutic Option ◽  
In Vitro Models ◽  
Metabolic Phenotype ◽  
Matched Pair

Abstract BACKGROUND Medulloblastoma is classified in 4 subgroups. Prognosis and therapeutic option was different from each subgroups. Thus, we need subgroup-specific in vitro models for investigating new therapeutic targets. Little established medulloblastoma cell-lines, which have been subgrouped is available. Especially, commercially available SHH type TP53 mutated cell-line is only DAOY. We established new cell lines 505CSC / 507FBS from the patient with SHH type with TP53 mutated MB. This matched pair cell line showed high expression of N-MYC in serum free conditioned medium. To know the functional role of N-MYC in MB, we used 507CSC and DAOY. MATERIAL AND METHODS Using chemical inhibitor of N-Myc in 507CSC and DAOY, proliferation assay, mRNA expression and measurements of ex-vivo metabolic phenotype were performed. RESULTS N-MYC inhibition leads to cell death in both cell lines. N-MYC regulated glucose, glutamine and methionine metabolism. Especially the targets were PKM2, GLS2, MAT2A, DNMT1 and 3A. CONCLUSION N-MYC is a target of therapy in a patient with SHH type TP53 mutated medulloblastoma.

scholarly journals Characterization of ghrelin receptor activity in a rat pituitary cell line RC-4B/C

2006 ◽  
Vol 37 (1) ◽  
pp. 51-62 ◽  
Author(s):  
H Douglas Falls ◽  
Brian D Dayton ◽  
Dennis G Fry ◽  
Christopher A Ogiela ◽  
Verlyn G Schaefer ◽  
...  
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Pituitary Cells ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue ◽  
Ghrelin Receptor ◽  
Intracellular Ca ◽  
Recombinant Cell

Ghrelin, a 28 amino acid, octanoylated peptide, is an endogenous ligand for the growth hormone secretagogue receptor (GHS-R). In addition to various endocrine functions, including stimulation of GH release, ghrelin has been characterized as an important regulator of energy homeostasis. Ghrelin administration has been shown to increase adiposity in rodents and stimulate food intake in humans. Studies suggest that these orexigenic effects are mediated primarily through GHS-R expression in hypothalamic and pituitary neuronal pathways. In this context, GHS-R has been recognized as a potential target for the treatment of GH deficiency and body weight disorders. Cell lines provide convenient in vitro systems to identify and characterize potential pharmacophores and to analyze GHS-R functional activity. While recombinant cell lines that overexpress GHS-R have served as effective research tools for these studies, such cell lines may differ in signaling response to ghrelin compared with hypothalamic or pituitary cells expressing GHS-R. We show here that a cell line derived from a rat anterior pituitary adenoma, RC-4B/C, expresses endogenous GHS-R as judged by reverse transcriptase-PCR. In a Ca2+mobilization assay, RC-4B/C cells demonstrate a dose-dependent increase in intracellular [Ca2+] on stimulation with rat ghrelin and a related peptide agonist, hexarelin (EC50, 1.0 nM and 1.7 nM respectively), but are unresponsive to treatment with inactive des-octanoyl rat ghrelin. A subclone, RC-4B/C.40, with a more robust and stable ghrelin response, was isolated from the parental population of cells to allow further analysis of GHS-R signal transduction. Using pertussis toxin and the phospholipase C inhibitor U-73122, we show that ghrelin signals through the Gq pathway in the RC-4B/C.40 cells. We also demonstrate that the ghrelin-induced rise of intracellular [Ca2+] in RC-4B/C.40 cells involves initial Ca2+release from intracellular stores followed by a sustained elevation that occurs via influx of extracellular Ca2+ through ion channels. In addition, unlike observations reported in recombinant cell systems, the RC-4B/C.40 cells do not exhibit a high level of GHS-R constitutive activity as determined in a phosphatidylinositol hydrolysis assay. Overall, the data presented here suggest that the RC-4B/C parental and RC-4B/C.40 cells provide novel in vitro systems for the characterization of GHS-R pharmacophores and ghrelin signaling.

scholarly journals In Vitro Studies on the Influence of Meloxicam on Cytotoxic Activity Induced by Risedronate Sodium in Canine (D-17) and Human (U-2 OS) Osteosarcoma Cell Lines

Animals ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 3135
Author(s):  
Dominik Poradowski ◽  
Izabela Janus ◽  
Aleksander Chrószcz ◽  
Bożena Obmińska-Mrukowicz
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Cytotoxic Effect ◽  
Tissue Level ◽  
Negative Control ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Osteosarcoma Cell ◽  
Apoptotic Effect

The study describes the cytotoxic effect against human and canine osteosarcoma (U-2 OS and D-17) cell lines induced by risedronate sodium and meloxicam per se and in combination. Both cell lines were prepared according to standard procedures for cell cultures studies. The cell viability was estimated in both cell lines treated with chosen concentrations of risedronate sodium and meloxicam. The apoptosis assessment was carried out using TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assay. EC50 values, computed for risedronate sodium and meloxicam cytotoxicity, showed comparable effects against the canine OS cell line in similar concentration of both drugs. In case of human OS, the stronger cytotoxic effect of risedronate sodium was proved. The EC50 values for meloxicam in both cell lines were, statistically, significantly different (* p < 0.05). Moreover, the cytotoxic effect of a combined administration of meloxicam and risedronate sodium in doses 100 µg/mL, compared with the negative control showed statistically significant differences. The human OS cell line was more resistant to both compounds than the canine OS cell line. The apoptotic effect in canine and human osteosarcoma triggered by risedronate sodium and meloxicam was statistically significant (p < 0.05). The cytotoxic effect induced with 100 µg/mL of risedronate sodium proved statistically significant differences between both tested cell lines compared to negative control. The results obtained with 10 and 100 µg/mL of meloxicam were not statistically significant. The study showed the synergic mechanism of action of risedronate sodium and meloxicam, but the concentrations used in vitro will not be possible to achieve in in vivo. Therefore, our results serve as basis only to design future studies on the tissue level.

scholarly journals CBMS-10 FUNCTIONAL ROLE OF MYCN IN SHH TYPE TP53 MUTATED MB’S METABOLISM

2019 ◽  
Vol 1 (Supplement_2) ◽  
pp. ii6-ii6
Author(s):  
Kiyotaka Yokogami ◽  
Takashi Watanabe ◽  
Shinji Yamashita ◽  
Asako Mizuguchi ◽  
Hideo Takeshima
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Functional Role ◽  
Ex Vivo ◽  
Therapeutic Option ◽  
In Vitro Models ◽  
Metabolic Phenotype ◽  
Matched Pair

Abstract BACKGROUND Medulloblastoma is classified in 4 subgroups. Prognosis and therapeutic option were different from each subgroups. Thus, we need subgroup-specific in vitro models for investigating new therapeutic targets. Little established medulloblastoma cell-lines, which have been subgrouped is available. Especially, commercially available SHH type TP53 mutated cell-line is only DAOY. We established new cell lines 505CSC / 507FBS from the patient with SHH type with TP53 mutated MB. This matched pair cell line showed high expression of MYCN in serum free conditioned medium. To know the functional role of N-MYC in MB, we used 507CSC and DAOY. MATERIAL AND METHODS Using chemical inhibitor of MYCN in 507CSC and DAOY, proliferation assay, mRNA expression and measurements of ex-vivo metabolic phenotype were performed. RESULTS MYCN inhibition leads to cell death in both cell lines. MYCN regulated glucose, glutamine and methionine metabolism. Especially the targets were PKM2, GLS2, MAT2A, DNMT1 and 3A. CONCLUSION MYCN is a target of therapy in a patient with SHH type TP53 mutated medulloblastoma.

scholarly journals Redounding of Cuscuta chinensis Lam. on BxPC-3, HepG2, and U2OS Human Cancer Cell Lines

2020 ◽  
Vol 10 (03) ◽  
pp. 354-359
Author(s):  
Basma Talib Al-Sudani ◽  
Nadia H. Mohammed ◽  
Fadia H. Al-Sultany
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
U2os Cell ◽  
Time Interval ◽  
Osteosarcoma Cell ◽  
Human Cancer Cell Lines ◽  
Cuscuta Chinensis

Objective: The present study was designed to investigate in vitro cytotoxic effect of aqueous extract from whole Cuscuta chinensis on human hepatocellular carcinoma (HepG2), biopsy xenograft of pancreatic carcinoma line-3 (BxPC-3), and children human bone osteosarcoma cell line (U2OS). Materials and Methods: The anticancer effectiveness of the methanol-watery extract of C. chinensis Lam. was determined by using methyl tetrazolium bromide test (MTT) assay against cancer cells by using suspensions of BxPC-3, HepG2, and U2OS cell lines. The inhibitory concentration (IC50) was tested for each cancer cell line. BxPC-3, HepG2, and U2OS cell line death percent after incubation with extract for 24, 48, and 72-hours interval was compared with cisplatin death percent. Results: The results showed that the IC50 of Cuscuta extract for BxPC-3, HepG2, and U2OS cell lines was 13, 6.5, and 0.73 μg/mL, respectively. The HepG2 cell line death%, when treated with 50 μg/mL Cuscuta extract at 24, 48, and 72-hour time interval, was 90.41, 91.45, and 92.93%, while cells were treated with 15 μg/mL cisplatin, the death percent was 88.8, 93.7, and 96.61%, respectively. The BxPC-3 cell line death%, when treated with 50 μg/mL Cuscuta extract, was 51.46, 83.37, and 91.28%, respectively, and when treated with 15 μg/mL cisplatin was 81.64, 88.02, and 96.67%, respectively. The U2OS cell line death%, when treated with 50 μg/mL Cuscuta extract, was 69.43, 69.75, and 88.89%, and was 74.1, 84.61, and 93.39%, respectively, when treated with 15 μg/mL cisplatin. Conclusion: The methanol-watery extract of C. chinensis Lam. may have a potential role as an adjunct therapy for cancers in the future.

scholarly journals Development and Characterisation of an in Vitro Model of Multiple Myeloma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4505-4505
Author(s):  
Thomas Lewis ◽  
Elisabeth Jane Walsby ◽  
Stephen Man ◽  
Christopher Fegan ◽  
Chris Pepper
Keyword(s):  
Multiple Myeloma ◽  
Cell Line ◽  
Cell Lines ◽  
In Vitro Model ◽  
Plastic Substrate ◽  
Osteosarcoma Cell ◽  
U937 Cells ◽  
Myeloma Cells ◽  
Vitro Model

Abstract Multiple myeloma is an incurable malignancy of terminally differentiated B-cells - also known as plasma cells. These malignant cells are extremely reliant on the bone marrow microenvironment for their growth and survival, as well as their acquired ability to resist therapeutic intervention. Consequently, maintaining primary myeloma cells in vitro remains a challenge. Patients suffering from this incurable disease often develop osteolytic lesions, due to an imbalance between osteoblasts and osteoclasts, which cause bone pain and a high frequency of fractures. This project aims to create a physiologically relevant in vitro model of myeloma that incorporates an osteoclast microenvironment. Osteoclasts normally work in concert with osteoblasts during bone tissue remodelling. In myeloma their activity predominates and is intrinsic to disease progression. It is now clear that osteoclasts also contribute to the survival of myeloma cells but the precise mechanism(s) for this remain unresolved. As a first step, we developed a model that can support and measure osteoclast function. We showed that the osteosarcoma cell line SAOS-2 was able to secrete a calcified matrix in a fashion similar to human osteoblasts. This was deposited on the plastic substrate following treatment with 300mM ascorbic acid and 10mM ß-glycerol phosphate for 28 days. Subsequently, the cells were removed from the mineralized plates and they were used to provide a base material to measure the resorption capacity of osteoclast-like cells and investigate how myeloma cells influence that activity. We next went on to develop and characterise an in vitro osteoclastic model using the myelo-monocytic U937 cell line. Treatment with 100nM PMA and 10nM calcitriol causes these cells to merge and form multi-nucleated (Figure 1A), TRAP positive (Figure 1B) and RANK positive cells. Culturing two different myeloma cell lines, H929 and RPMI-8226, in co-culture with the osteoclast-like cells for a period of 48 hours revealed two unique sub-populations of CD138bright and CD138dim myeloma cells. Phenotypic analysis of these distinct populations showed that they expressed similar levels of CD38 but the CD138dim cells showed a significant upregulation of CD69 (p≤0.05) in both cell lines as a result of co-culture with differentiated U937 osteoclast-like cells. This data indicates that osteoclast-like U937 cells can activate a subset of myeloma cells and may provide a means of sustaining primary myeloma cells in vitro. We are currently performing RNA-seq experiments to try to understand why only a subset of cells respond to this stimulus. We will then go on to establish whether primary myeloma cells derived from patients show similar responses when co-cultured under the same conditions. Figure 1: U937 cells have the capacity to form large multinucleated osteoclast-like cells that express tartrate resistant alkaline phosphatase (TRAP). A. Representative brightfield images coupled with images of DAPI staining following treatment with PMA and calcitriol reveals that U937 cells can become adherent and merge with one another to form large, multinucleated cells. B. Representative images of TRAP (purple) staining illustrate that these osteoclast-like U937 cells are also able to express TRAP following treatment. Disclosures Fegan: Acerta Pharma: Research Funding. Pepper:Cardiff University: Patents & Royalties: Telomere measurement patents.

Identification of Driver Genes and Key Pathways of Osteosarcoma Shows K-7174 As a Novel Anti-osteosarcoma Drug by Inhibiting VCAM1

2020 ◽  
Author(s):  
Zhaoyu Fu ◽  
Jing Yu ◽  
Yan Liu ◽  
Bo Wu ◽  
Long Cheng ◽  
...  
Keyword(s):  
Cell Lines ◽  
Antigen Processing ◽  
Interaction Network ◽  
Mg63 Cell ◽  
Migration And Invasion ◽  
Therapeutic Drug ◽  
Osteosarcoma Cell ◽  
Current Standard ◽  
Driver Genes

Abstract BackgroundOsteosarcoma is one of the leading causes in cancer-related death of children and adolescents. However current standard therapeutic strategy, surgery combined with neoadjuvant chemotherapy is very limited in effects. As big data mining and analysis using bioinformatics method has been applied in the diagnosis and treatment of many cancers, we want to use bioinformatic combined with experimental assays to found new molecular targets and test new drug for osteosarcoma.MethodsThe gene chip of osteosarcoma samples constructed by Richter GH et al were downloaded from the Gene Expression Omnibus (GEO) database, Gene Ontology analysis (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed on differential expression genes which screened by bioinformatics methods.Protein-protein interaction network was constructed by suing STRING database to found hub gene. Combined with pertinent literature, genes of interest and corresponding drug was selected. Series of experiments were performed on the osteosarcoma cell lines in vitro, involved cell viability test, colony formation assay, migratory and invasive tests, western blot as well.ResultsA total of 1069 DEGs were obtained from data, including 375 up-regulated genes and 694 down-regulated genes. Differentially expressed genes mainly involve biological processes such as cellular immune function, such as interferon-gamma-mediated signaling pathway and antigen processing and presentation of peptide. Among top 20-ranked degree hug gene evaluated by PPI network, vascular cell adhesion molecule-1(VCAM1) was picked out. An VCAM1 inhibitor K-7174 was treated in U2OS and MG63 cell lines. In vitro experiments have shown that K-7174 can inhibit the proliferation, migration and invasion of osteosarcoma, the protein expression of VCAM1was also decreased by K-7174.ConclusionsVCAM1 could be a potential target for osteosarcoma and K-7174 promises to be a therapeutic drug after more nuanced evaluation in animal and clinical trials.

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