Dataset Information

Overexpression of metadherin mediates metastasis of osteosarcoma by regulating epithelial-mesenchymal transition.

ABSTRACT:

Objectives

Osteosarcoma (OS) is one of the most common primary malignant bone tumours of childhood and adolescence, and is characterized by high propensity for metastasis (specially to the lung), which is the main cause of death. However, molecular mechanisms underlying metastasis of OS are still poorly understood.

Materials and methods

Metadherin (MTDH) was identified to be significantly upregulated in OS tissues that had metastasized compared to OS without metastasis, using a two-dimensional approach of electrophoresis, coupled with mass spectrometry. To understand the function of MTDH in OS, OS cell lines U2OS and SOSP-M were transfected with retroviral shRNA vector against MTDH.

Results

It was found that metastatic propensity as well as cell proliferation were significantly reduced in both U2OS and SOSP-M. Migration and invasion of U2OS and SOSP-M cells were significantly lower after knock-down of MTDH. In addition, epithelial-mesenchymal transition (EMT) was reduced after knock-down of MTDH. Clinicopathologically, overexpression of MTDH was significantly associated with metastasis and poor survival of patients with OS.

Conclusion

Taken together, our results demonstrate that MTDH mediated metastasis of OS through regulating EMT. This could be an ideal therapeutic target against metastasis of OS.

SUBMITTER: Tang J

PROVIDER: S-EPMC6495483 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Publications

Overexpression of metadherin mediates metastasis of osteosarcoma by regulating epithelial-mesenchymal transition.

Tang J J Shen L L Yang Q Q Zhang C C

Cell proliferation 20140901 5

<h4>Objectives</h4>Osteosarcoma (OS) is one of the most common primary malignant bone tumours of childhood and adolescence, and is characterized by high propensity for metastasis (specially to the lung), which is the main cause of death. However, molecular mechanisms underlying metastasis of OS are still poorly understood.<h4>Materials and methods</h4>Metadherin (MTDH) was identified to be significantly upregulated in OS tissues that had metastasized compared to OS without metastasis, using a tw ...[more]

PMID: 25174891

Similar Datasets

Project description:Osteosarcoma (OS) is a rare type of tumor and mostly occurs in children and adolescents. Approximately 10‑25% of patients with OS have lung metastases, and lung damage caused by lung metastasis is the main cause of mortality. Therefore, studying the growth and metastasis of OS is key in reducing OS mortality and improving prognosis. The expression of long non‑coding RNA (lncRNA) cancer susceptibility 15 (CASC15) in OS patients or OS cell lines were quantified by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). The expression of vimentin, E‑cadherin, N‑cadherin, and cyclin D were detected by RT‑qPCR and western blotting. Mice were injected with OS cell lines via the tail vein to observe tumor formation in the lung. CCK‑8 and EdU assays were utilized to evaluate cell proliferation. Both Ttranswell assay and cell scratch test detected cell migration. The results revealed that lncRNA‑CASC15 was highly expressed in clinical samples and OS cells. In vitro verification experiments revealed that CASC15 promoted the growth of OS cells. Rescue experiments demonstrated that CASC15 affected the cell cycle by activating the Wnt/β‑catenin pathway, thereby promoting cell proliferation. Furthermore, the transfection dose test indicated that lentiviruses expressing various doses of CASC15‑overexpression (oe‑CASC15) altered the proliferation and migration status of OS cells. CASC15 promoted OS cell metastasis both in vivo and in vitro. The overexpression of CASC15 revealed that the occurrence of metastasis was also related to the Wnt/β‑catenin pathway. The western blotting results revealed that CASC15 could lead to β‑catenin entering the nucleus via the Wnt pathway to promote the epithelial‑mesenchymal transition (EMT) of OS cells. To sum up, CASC15 promoted the proliferation of OS cells in vitro and the growth of OS xenograft tumors in vivo. Moreover, CASC15 promoted the entry of β‑catenin into the nucleus, thus activating the Wnt pathway and subsequently promoting the EMT of OS cells.

Dataset Information

Overexpression of metadherin mediates metastasis of osteosarcoma by regulating epithelial-mesenchymal transition.

Objectives

Materials and methods

Results

Conclusion

Publications

Overexpression of metadherin mediates metastasis of osteosarcoma by regulating epithelial-mesenchymal transition.

Similar Datasets

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