Gene expression profiles of human osteosarcoma cell sublines with different pulmonary metastatic potentials

Chen, Xiang; Yang, Tao; Qiu, Xiuchun; Ji, Zhen-gang; Li, Cunxiao; Long, Hua; Zhou, Yong; Ma, Baoan; Ma, Qiang; Zhang, Xianzhi; Fan, Qingyu

doi:10.4161/cbt.11.2.13966

Cited by 12 publications

(11 citation statements)

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“…Huang CY found that human OS cell lines had significantly increased expression of SDF-1 and CXCR4 [29]. Our previous study confirmed that the expression level of CXCR4 was significantly different in various OS cell lines with pulmonary metastatic potential [30]. Therefore, we analyzed the correlation between the high expression of both HIF-1α and CXCR4 and clinicopathologic significance in human OS samples.…”

Section: Discussionmentioning

confidence: 77%

Hypoxia Promotes Migration and Induces CXCR4 Expression via HIF-1α Activation in Human Osteosarcoma

et al. 2014

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BackgroundCellular adaptation to a hypoxic microenvironment is essential for tumor progression and is largely mediated by HIF-1α through coordinated regulation of hypoxia-responsive genes. The chemokine SDF-1α and its unique receptor CXCR4 have been implicated in organ-specific metastases of many cancers. In this study, we investigated the response of osteosarcoma cells to hypoxia and the expression of CXCR4 and HIF-1α in human osteosarcoma specimens and explored the roles of CXCR4 and HIF-1α in the cell migration process.Methodology/Principal FindingsWe performed immunohistochemistry, immunocytochemistry, quantitative real-time PCR, Western blots and fluorescent reporter assays to evaluate the correlation between CXCR4 and HIF-1α expression in human osteosarcoma specimens or SOSP-9607 cells under normoxic and hypoxic conditions. Transwell assays were used to assess cell migration under different conditions. Exposure of SOSP-9607 cells to hypoxic conditions resulted in significantly increased migration. When SOSP-9607 cells were subjected to hypoxic conditions, the mRNA and protein levels of CXCR4 were significantly increased in a time-dependent manner. Moreover, siHIF-1α significantly decreased the mRNA and protein levels of CXCR4 under hypoxia, whereas pcDNA-HIF-1α significantly increased the mRNA and protein levels of CXCR4 under normoxia. A luciferase reporter gene study showed that siHIF-1α reduced pGL3-CXCR4 luciferase activity. Furthermore, coexpression of HIF-1α and CXCR4 was significantly higher in patients with distant metastasis compared with those without metastasis.Conclusions/SignificanceThe hypoxia-HIF-1α-CXCR4 pathway plays a crucial role during the migration of human osteosarcoma cells, and targeting this pathway might represent a novel therapeutic strategy for patients suffering from osteosarcoma.

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Section: Discussionmentioning

confidence: 77%

Hypoxia Promotes Migration and Induces CXCR4 Expression via HIF-1α Activation in Human Osteosarcoma

et al. 2014

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“…In the present study, we established a pair of OS cell lines with different metastatic potentials named F5M2 (highly metastatic) and F4 (lowly metastatic) [ 19 ]. Gene expression and proteomic profiling were performed subsequently to identify the metastasis associated molecules [ 20 , 21 ]. To further analyze the regulation mechanism regarding gene-microRNA-protein network.…”

Section: Resultsmentioning

confidence: 99%

MicroRNA profiling identifies MiR-195 suppresses osteosarcoma cell metastasis by targeting CCND1

et al. 2015

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Metastasis is a leading cause of mortality for osteosarcoma patients. The molecular pathological mechanism remains to be elucidated. In the previously study, we established two osteosarcoma cell lines with different metastatic potentials. Differential expressed genes and proteins regarding metastatic ability have been identified. MicroRNAs are important regulators in tumorigenesis and tumor progression. In this study, microRNA microarray was used to assess the differential expressed miRNAs level between these two cell lines. One of the top ranked miRNAs-miR-195 was identified highly expressing in lowly metastatic cells. It was showed that over-expression of miR-195 substantially inhibits migration and invasion of osteosarcoma cells in vitro and pulmonary metastasis formation in vivo. Meanwhile, CCND1 was identified as the target gene of miR-195 and further studied. More importantly, Using real-time PCR, we evaluated the expression of miR-195 and CCND1 in osteosarcoma samples from 107 frozen biopsy tissues and 99 formalin- or paraformalin-fixed, paraffin-embedded (FFPE) tissues. Results indicated lowly expressed miR-195 or highly CCND1 correlated with positive overall survival and their expression inverse relate to each other. In summary, our study suggests miR-195 function as a tumor metastasis suppressor gene by down-regulating CCND1 and can be used as a potential target in the treatment of osteosarcoma.

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“…Comparisons of high- and low-metastatic osteosarcoma cell lines using microarrays have identified several differentially expressed genes related to growth arrest and apoptosis [11], as well as adherence, motility, and/or invasiveness [12]. Another study identified two genes not previously linked to osteosarcoma, epiregulin ( EREG ) and carbohydrate (N-acetylglucosamine-6-O) sulfotransferase 2 ( CHST2 ), both predictive for survival [13]. A recent gene expression profiling of osteosarcoma patients who did and did not develop metastasis revealed a number of differentially expressed genes related to immunological functions, particularly macrophages [14].…”

Section: Introductionmentioning

confidence: 99%

Global Gene Expression Profiling of Human Osteosarcomas Reveals Metastasis-Associated Chemokine Pattern

Namløs

Kresse

Müller

et al. 2012

Sarcoma

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Global gene expression analysis was performed on a panel of 23 osteosarcoma samples of primary and metastatic origin using the Applied Biosystems Gene Expression Array System. When comparing the primary tumours with the metastases, we found a significantly increased expression of genes involved in immunological processes, for example coding for cytokines and chemokines, in the metastatic samples. In addition, a comparison of the gene expression in primary samples from patients with or without metastases demonstrated that patients who later developed metastases had high expression of the chemokine (C-X-C motif) receptor 4 (CXCR4), similar to the metastatic samples, suggesting that these signal molecules play an important role in promoting metastasis. Increased knowledge of mechanisms and interactions between specified molecular signalling pathways in osteosarcomas could lead to a more rational strategy for development of targeted therapy.

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Gene expression profiles of human osteosarcoma cell sublines with different pulmonary metastatic potentials

Cited by 12 publications

References 10 publications

Hypoxia Promotes Migration and Induces CXCR4 Expression via HIF-1α Activation in Human Osteosarcoma

Hypoxia Promotes Migration and Induces CXCR4 Expression via HIF-1α Activation in Human Osteosarcoma

MicroRNA profiling identifies MiR-195 suppresses osteosarcoma cell metastasis by targeting CCND1

Global Gene Expression Profiling of Human Osteosarcomas Reveals Metastasis-Associated Chemokine Pattern

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