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Oxidized low density lipoprotein receptor 1 promotes lung metastases of osteosarcomas through regulating the epithelial-mesenchymal transition.

ABSTRACT: BACKGROUND:Oxidized low density lipoprotein receptor 1 (OLR1), a type II membrane protein, has been identified as receptor for oxidized low-density lipoprotein. The current study firstly provided evidence that OLR1 regulated EMT and thus promoted lung metastases in osteosarcoma (OS). METHOD:All relevant experiments were conducted according to the manufacturer's protocols. In vivo tumor xenograft experiments were carried out in 6- to 16-week-old mice, then maintained in our animal facility under pathogen-free conditions in accordance with the Institutional Guidelines and approval by local authorities. For the use of the clinical materials for research purposes, prior patient's consent and approval from the Institute Research Ethics Committee were obtained. All statistical analyses were performed using IBM SPSS Statistics 22.0 for Windows. RESULT:Microarrays were adopted to explore the underlying epigenetic mechanisms related to metastasis. 11 genes were identified among total 26,890 differentially expressed genes. After validated in paired primary and metastatic tissues, OLR1 was selected in the current study. The expression levels of OLR1 were tested in 4 widely used cell lines. Cell proliferation, migration and invasion could be enhanced when OLR1 was overexpressed. OLR1 overexpression also triggered G1 to S?+?G2 phases of cell cycle. Accordingly, cell proliferations, migration and invasion would be reduced when OLR1 was silenced. OLR1-silencing blocked G1 to S?+?G2 phases of cell cycle. Also, OLR1 silencing effectively suppressed local tumor carcinogenesis and lung metastases in vivo. Moreover, silencing OLR1 repressed the expression of mesenchymal markers (Snail, Twist, and N-cadherin), but induced an epithelial marker (E-cadherin). CONCLUSION:This study indicated a novel molecular mechanism involving the role of OLR1 in lung metastases of osteosarcoma, strengthened the correlation between OLR1 and lung metastases.

SUBMITTER: Jiang L

PROVIDER: S-EPMC6852786 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Oxidized low density lipoprotein receptor 1 promotes lung metastases of osteosarcomas through regulating the epithelial-mesenchymal transition.

Jiang Long L Jiang Shanshan S Zhou Wenjie W Huang Jia J Lin Yongbin Y Long Hao H Luo Qingquan Q

Journal of translational medicine 20191112 1

<h4>Background</h4>Oxidized low density lipoprotein receptor 1 (OLR1), a type II membrane protein, has been identified as receptor for oxidized low-density lipoprotein. The current study firstly provided evidence that OLR1 regulated EMT and thus promoted lung metastases in osteosarcoma (OS).<h4>Method</h4>All relevant experiments were conducted according to the manufacturer's protocols. In vivo tumor xenograft experiments were carried out in 6- to 16-week-old mice, then maintained in our animal ...[more]

PMID: 31718700

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Project description:ObjectiveTo explore the role of vasohibin-2 (VASH2) in regulation of proliferation and metastasis of cervical cancer cells.MethodsWe analyzed the differentially expressed genes between cervical cancer cells with flotillin-1 overexpression and knockdown by RNA-seq combined with analysis of public databases. The expression levels of VASH2 were examined in normal cervical epithelial cells (HcerEpic), cervical cancer cell lines (HeLa, C-33A, Ca ski, SiHa and MS751) and fresh cervical cancer tissues with different lymph node metastasis status. We further tested the effects of lentivirus-mediated overexpression and interference of VASH2 on proliferation, migration, invasion and lymphatic vessel formation of the cervical cancer cells and detected the expression levels of key epithelial-mesenchymal transition (EMT) markers and TGF-β mRNA.ResultsRNA-seq and analysis of public databases showed that VASH2 expression was significantly upregulated in cervical cancer cells exogenously overexpressing flotillin-1 (P < 0.05) and downregulated in cells with flotillin-1 knockdown (P < 0.05), and was significantly higher in cervical cancer tissues with lymph node metastasis than in those without lymph node metastasis (P < 0.01). In cervical cancer cell lines Ca Ski, SiHa, and MS751 and cervical cancer tissue specimens with lymph node metastasis, VASH2 expression was also significantly upregulated as compared with HcerEpic cells and cervical cancer tissues without lymph node metastasis (P < 0.05). Exogenous overexpression of VASH2 significantly promoted proliferation, migration, invasion and lymphatic vessel formation of cervical cancer cells, whereas these abilities were significantly inhibited in cells with VASH2 knockdown (P < 0.05). The cervical cancer cells overexpressing VASH2 showed significant down- regulation of e-cadherin and up- regulation of N-cadherin, Vimentin and VEGF-C, while the reverse changes were detected in cells with VASH2 knockdown (P < 0.05). TGF-β mRNA expression was significantly up-regulated in cervical cancer cells overexpressing VASH2 and down-regulated in cells with VASH2 knockdown (P < 0.001).ConclusionFlotillin-1 may participate in TGF-β signaling pathway-mediated EMT through its down-stream target gene VASH2 to promote the proliferation, migration, invasion and lymphatic vessel formation of cervical cancer cells in vitro.

Dataset Information

Oxidized low density lipoprotein receptor 1 promotes lung metastases of osteosarcomas through regulating the epithelial-mesenchymal transition.

Publications

Oxidized low density lipoprotein receptor 1 promotes lung metastases of osteosarcomas through regulating the epithelial-mesenchymal transition.

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