Current concepts on pathogenesis and biology of metastatic osteosarcoma tumors

Poletajew, Sławomir; Fus, Łukasz; Wasiutyński, Aleksander

doi:10.5604/15093492.971038

Cited by 41 publications

(33 citation statements)

References 38 publications

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“…It is the most common primary bone malignancy in childhood and adolescence (1)(2)(3). OS is primarily a malignant neoplasm of the long bones, with the greatest predilection for the metaphyses of the distal femur and proximal tibia (4).…”

Section: Introductionmentioning

confidence: 99%

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Activin A regulates proliferation, invasion and migration in osteosarcoma cells

Jun

Fan

et al. 2015

Molecular Medicine Reports

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Activin A is a member of the TGF‑β superfamily. Previous studies have demonstrated that activin A exhibited pluripotent effects in several tumours. However, the roles of activin A signaling in osteosarcoma pathogenesis have not been previously investigated. Therefore, the present study aimed to investigate the effects of activin A on osteosarcoma cell proliferation, invasion and migration. Firstly, the expression of activin A in osteosarcoma cell lines (MG63, SaOS‑2 and U2OS) and a human osteoblastic cell line (hFOB1.19) was detected using reverse transcription quantitative polymerase chain reaction and western blotting. Activin A was upregulated in osteosarcoma cell lines compared with hFOB1.19 cells. To investigate the effects of activin A on osteosarcoma cell proliferation, invasion and migration, MG63 cells were generated in which activin A was either overexpressed or depleted. MTT staining, propidium iodide staining and a Transwell assay were used to analyze the cell cycle, proliferation, invasion and migration of MG63 cells, respectively. The results of the present study revealed that the abilities of proliferation, invasion and migration were suppressed in MG63 cells in which activin A was depleted, while they were enhanced in activin A-overexpressing cells. In conclusion, the results of the present study suggested that activin A may facilitate proliferation, invasion and migration of osteosarcoma cells, and it may therefore be a potential target for the treatment of osteosarcoma.

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Section: Introductionmentioning

confidence: 99%

“…To date, the molecular mechanisms behind osteosarcoma development and metastasis have remained elusive. Therefore, broadening our understanding of the pathogenesis and biology of metastatic osteosarcoma is a key factor for improving treatment results and identifying potential therapeutic targets (2).…”

Section: Introductionmentioning

confidence: 99%

Activin A regulates proliferation, invasion and migration in osteosarcoma cells

Jun

Fan

et al. 2015

Molecular Medicine Reports

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“…Furthermore, the treatment for all types is similar (4). The prognosis of this disease is poor despite the use of multimodal therapy, including surgery, radiotherapy and chemotherapy (5,6). Progression to metastatic disease is the predominant cause of treatment failure, while the cellular and molecular mechanisms defining the biological behavior of osteosarcoma cells are poorly understood (6).…”

Section: Introductionmentioning

confidence: 99%

Increased Six1 expression is associated with poor prognosis in patients with osteosarcoma

2017

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Sine oculis homeobox homolog 1 (Six1) is an evolutionarily conserved transcription factor that acts as master regulator of development and is frequently dysregulated in various types of cancer. Six1 has been demonstrated to be upregulated in human osteosarcoma cell lines compared with osteoblastic cell lines. However, the association of Six1 expression with the progression and prognosis of osteosarcoma patients remains unclear. The purpose of the present study was to investigate the association between Six1 expression and the clinicopathological characteristics and prognosis of osteosarcoma. Six1 protein was detected by immunohistochemistry in a series of 100 osteosarcoma patients, and Kaplan-Meier survival analysis was performed to assess prognosis. The results revealed that increased Six1 protein expression was prevalent in osteosarcoma and was significantly associated with Enneking stage (P=0.002) and tumor size (P=0.010). Additionally, according to the log-rank test and Cox regression model, expression of Six1 is indicated to be an independent prognostic factor in osteosarcoma patients. In summary, positive expression of Six1 protein is closely associated with the tumor progression and poor survival of osteosarcoma patients. The results suggest that Six1 is a overexpressed in individuals with poor prognosis, and may thus be used as a prognostic biomarker in patients with osteosarcoma.

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“…Despite the considerable increase in the survival rate of patients with osteosarcoma to 65%–75%, due to great advances in surgical technology and combined therapeutic strategies, the survival of patients with pulmonary metastases and advanced clinical stage remains poor 3. Therefore, accumulating attempts have been made to identify the prognostic factors for survival of patients with osteosarcomas and to identify patients with a high risk of developing recurrence or metastases from those with a low risk 4. Several clinicopathological characteristics, such as tumor size, tumor grade, response to chemotherapy, and status of metastasis, have been used as prognostic factors for patients with osteosarcomas,5 but their sensitivities and specificities are not satisfactory, implying that several genetic or molecular events may be implicated in the tumorigenesis of this malignancy.…”

Section: Introductionmentioning

confidence: 99%

Upregulation of micro-ribonucleic acid-128 cooperating with downregulation of PTEN confers metastatic potential and unfavorable prognosis in patients with primary osteosarcoma

Tian¹,

Guo²,

Yu³

et al. 2014

OTT

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ObjectiveAbnormal expression of micro-ribonucleic acid (miRNA [miR])-128 has been observed in various human cancer types, and its validated target genes are implicated in cancer-related cellular processes, such as cell proliferation, differentiation, and apoptosis. Especially, it has been demonstrated that miR-128 may play an important role in the proliferation of human osteosarcoma cells in vitro by directly inhibiting PTEN, which functions as a tumor suppressor in this malignancy. In the current study, we investigated the involvement of miR-128 and its target gene PTEN in tumor progression and prognosis in patients with primary osteosarcoma.Materials and methodsExpression levels of miR-128 and PTEN messenger RNA in osteosarcoma and noncancerous bone tissues obtained from 100 patients with primary osteosarcoma were detected by quantitative real-time polymerase chain reaction.ResultsExpression levels of miR-128 and PTEN messenger RNA in osteosarcoma tissues were significantly higher and lower, respectively, than those in noncancerous bone tissues (both P<0.001). In addition, high miR-128 expression and low PTEN expression, alone (miR-128-high or PTEN-low) or combined (miR-128-high/PTEN-low), were all dramatically associated with poor response to chemotherapy and positive metastasis. More importantly, the associations of miR-128-high/PTEN-low expression with these clinicopathological parameters were more significant than miR-128-high or PTEN-low alone. Finally, miR-128 expression, PTEN expression, miR-128/PTEN expression, the response to chemotherapy and the metastatic status were all identified as independent prognostic factors for overall survival and disease-free survival.ConclusionThese findings indicate for the first time that the deregulation of miR-128 and its target gene PTEN may be involved in the aggressive progression of human osteosarcoma. Notably, the upregulation of miR-128 cooperating with the downregulation of PTEN may confer an unfavorable prognosis in patients with this malignancy.

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Current concepts on pathogenesis and biology of metastatic osteosarcoma tumors

Cited by 41 publications

References 38 publications

Activin A regulates proliferation, invasion and migration in osteosarcoma cells

Activin A regulates proliferation, invasion and migration in osteosarcoma cells

Increased Six1 expression is associated with poor prognosis in patients with osteosarcoma

Upregulation of micro-ribonucleic acid-128 cooperating with downregulation of PTEN confers metastatic potential and unfavorable prognosis in patients with primary osteosarcoma

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