Osteosarcoma in Preadolescent Patients

Rytting, Michael; Pearson, Peggy; Raymond, A. Kevin; Ayala, Alberto G.; Murray, John A.; Yasko, Alan W.; Johnson, Mai; Jaffe, Norman

doi:10.1097/00003086-200004000-00007

Cited by 66 publications

(37 citation statements)

References 24 publications

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“…It arises from primitive transformed cells of mesenchymal origin (and thus a sarcoma), exhibits osteoblastic differentiation and produces malignant osteoid (1). The main symptoms of OS are local pain and swelling (2,3). More than half of all OS cases arise in the long bones of the limbs, particularly the knee (4).…”

Section: Introductionmentioning

confidence: 99%

Analysis of the molecular mechanism of osteosarcoma using a bioinformatics approach

Yang

Wang

2016

Oncology Letters

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Abstract. The aim of this study was to explore the underlying molecular mechanism related to the process and progression of osteosarcoma (OS). The differentially expressed genes (DEGs) were downloaded from the Gene Expression Omnibus database. The pathway and gene ontology (GO) enrichment analysis, as well as transcription factor, tumor-associated gene and tumor suppressor gene analyses were performed to investigate the functions of DEGs. Next, the protein-protein interaction (PPI) network was constructed and module analysis was further assessed by cluster analysis with the overlapping neighborhood expansion (Cluster ONE) cytoscape plug-in. A total of 359 upregulated and 614 downregulated DEGs were identified to be differentially expressed between OS samples and normal controls. Pathways significantly enriched by DEGs included the focal adhesion and chromosome maintenance pathways. Significant GO terms were cell adhesion, cell cycle and nucleic acid metabolic processes. The upregulated PPI network was constructed with 170 nodes and the downregulated PPI network was constructed with 332 nodes. Breast-ovarian cancer gene 1 (BRCA1), melanocyte-stimulating hormone 2 (MSH2), cyclin D1 (CCND1) and integrin α5 (ITGA5) were identified to be hub proteins in PPI. In conclusion, the dysregulated genes played key roles in the progression of OS. Cell adhesion is a significant biological process in OS development, and the genes BRCA1, MSH2, CCND1 and ITGA5 may be potential targets in the therapy of OS.

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Section: Introductionmentioning

confidence: 99%

Analysis of the molecular mechanism of osteosarcoma using a bioinformatics approach

Yang

Wang

2016

Oncology Letters

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“…2 Along with the development of combination treatment (adjuvant chemotherapy, surgery and neoadjuvant chemotherapy), the prognosis of osteosarcoma has gradually improved over the past 30 y. [3][4][5] However, for patients who present with metastatic disease or whose tumor recurs, the survival was less than 30% and 20%, respectively. 6 This emphasizes the need for new therapeutic targets and approaches for osteosarcoma.…”

Section: Introductionmentioning

confidence: 99%

RNAi-mediated silencing of AQP1 expression inhibited the proliferation, invasion and tumorigenesis of osteosarcoma cells

Liu

et al. 2015

Cancer Biology & Therapy

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Aquaporin 1 (AQP1), a member of water channel proteins, functions as a water-selective transporting protein in cell membranes. In recent years, AQP1 has been found to be overexpressed in various tumors. However, the molecular mechanism underlying the biological function of AQP1 in osteosarcoma is still unclear. This study was aimed at elucidating the roles of AQP1 in regulating the biological behavior of osteosarcoma cells. In this study, we found that AQP1 mRNA was elevated in osteosarcoma tissue. High level of AQP1 was associated with poor prognosis in osteosarcoma. Then, we found that knockdown of AQP1 in osteosarcoma cells, U2OS or MG63 cells inhibited cell proliferation and significantly increased cells population in G1 phase. Additionally, suppressing AQP1 expression in osteosarcoma cells dramatically induced cell apoptosis. We also found that down-regulation of AQP1 significantly inhibited cell adhesion and invasion. More importantly, AQP1 knockdown inhibited tumor growth in vivo and prolonged the survival time of nude mice. Gene set enrichment analysis (GSEA) showed that transforming growth factor-b (TGF-b) signaling pathway and focal adhesion genes was correlatively with AQP1 expression. In addition, real time PCR and western blot analysis revealed that expression of TGF-b1/TGF-b2, RhoA and laminin b 2 (LAMB2) was remarkably impaired by AQP1 silencing. In conclusion, AQP1 may be a useful diagnosis and prognosis marker for osteosarcoma. AQP1 knockdown can effectively inhibit cell proliferation, adhesion, invasion and tumorigenesis by targeting TGF-b signaling pathway and focal adhesion genes, which may serve a promising therapeutic strategy for osteosarcoma.

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“…In most cases, OS originates from the metaphysis of long bones and is mostly found in areas of rapid growth in children, i.e., the knees and shoulders and the long bones of the arms and legs (2). OS is highly aggressive and primarily metastasizes to the lungs (3).…”

Section: Introductionmentioning

confidence: 99%

Cytoprotective role of autophagy during paclitaxel-induced apoptosis in Saos-2 osteosarcoma cells

Kim

Lee

Kim

et al. 2013

International Journal of Oncology

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Abstract. Osteosarcoma (OS) is the most common primary malignant bone cancer in children and adolescents. Although paclitaxel (PCX) has been considered one of the most important cancer chemotherapeutic drugs, the current protocols for OS treatment do not incorporate this agent. Therefore, the purpose of this study was to evaluate the induction of cell death in OS cells after exposure to PCX, to identify the cell death mechanism(s) activated by PCX and to investigate whether autophagy is associated with PCX-induced apoptosis. The results of the present study confirmed that exposure to low PCX concentrations can induce apoptotic cell death in Saos-2 cells; furthermore, caspase-3 activation, PARP degradation and XIAP downregulation were observed in combination with PCX-induced apoptosis. The potential involvement of mitochondrial events (intrinsic apoptotic pathway) in PCX-induced apoptosis in OS cells was verified by the alteration (depolarization) of mitochondrial membrane potential. In addition, pretreatment with 3-methyladenine (3-MA), a specific inhibitor of autophagy, significantly increased PCX-induced apoptotic cell death in Saos-2 cells. The augmentation of PCX-induced apoptosis by 3-MA was accompanied by increase in the cytochrome c release from the mitochondria, caspase-3 activity and XIAP downregulation, which suggests that inhibiting autophagy further stimulates the PCX-induced mitochondrionrelated (intrinsic) apoptotic pathway by provoking caspase-3 activation. Thus, autophagy observed during PCX-induced apoptosis in Saos-2 OS cells represents the role of cytoprotection in cellular homeostatic processes. In conclusion, the results of this study revealed that PCX exposure effectively induces OS cell death by apoptosis associated with the mitochondrial-mediated caspase-dependent pathway. PCX can increase autophagic activity and suppressing autophagy enhances PCX-induced apoptosis in OS cells. Therefore, it is suggested that combination treatment involving low-dose PCX therapy and autophagy inhibitor therapy could be an effective and potent strategy for improved chemotherapy for OS in the near future.

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Osteosarcoma in Preadolescent Patients

Cited by 66 publications

References 24 publications

Analysis of the molecular mechanism of osteosarcoma using a bioinformatics approach

Analysis of the molecular mechanism of osteosarcoma using a bioinformatics approach

RNAi-mediated silencing of AQP1 expression inhibited the proliferation, invasion and tumorigenesis of osteosarcoma cells

Cytoprotective role of autophagy during paclitaxel-induced apoptosis in Saos-2 osteosarcoma cells

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