Abstract
BackgroundOsteosarcoma is generally reported among younger individuals and has a very poor prognosis, particularly for the development of metastasis. However, more effective metastatic biomarkers and therapeutic methods are absent. Monocyte chemoattractant protein-1 (MCP-1) is involved in cancer progression and inflammatory recruitment. Although previous studies have reported higher serum MCP-1 levels in patients with osteosarcoma, the role of MCP-1 in osteosarcoma progression remains to be addressed.MethodsThe osteosarcoma cell migratory ability was assessed by transwell migration assay. The MCP-1 and MMP-9 expression levels were analyzed by Western blot and qPCR. The signal activation was conducted by Western blot. The in vivo mouse experiment and tumor tissue array were performed to confirm our findings in vitro.ResultsThe present study demonstrates that MCP-1 regulates cell mobility through matrix metalloproteinase (MMP)-9 expression in osteosarcoma cells. Moreover, MCP-1 promotes MMP-9 expression, cell migration, and cell invasion by mediating CCR2, c-Raf, MAPK, and AP-1 signal transduction. Using MCP-1 knockdown stable cell lines, we found that MCP-1 knockdown reduces MMP-9 expression and cell mobility. Finally, we found high MCP-1 expression levels in osteosarcoma specimens.ConclusionsOur results provide prognostic value of MCP-1 in osteosarcoma by promoting MMP-9 expression.
Highlights
Osteosarcoma is generally reported among younger individuals and has a very poor prognosis, for the development of metastasis
The higher the generation was, the Matrix metalloproteinases (MMPs)-9 was involved in Monocyte chemoattractant protein-1 (MCP-1)-mediated osteosarcoma cell migration Studies have revealed that MMPs including MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-12, and MMP-13 are significantly related to osteosarcoma metastasis and poor prognosis [19, 33,34,35,36,37,38]
To identify the mediator of MCP-1-promoted osteosarcoma migration, we further examined the expression of MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-12, and MMP-13 mRNA under MCP-1 stimulation (Fig. 2a)
Summary
Osteosarcoma is generally reported among younger individuals and has a very poor prognosis, for the development of metastasis. More effective metastatic biomarkers and therapeutic methods are absent. Osteosarcoma is the most common primary bone malignancy, and it accounts for 30 to 80% of primary skeletal sarcomas [1]. Osteosarcoma diagnoses are classified into four grades according to the histological degree of diffusion and differentiation; higher grades indicate more aggressive malignant neoplasms [2]. Metastasis is one of the leading causes of poor prognosis in patients with osteosarcoma; only 20% of the patients survive for more than 5 years [6]. An increasing number of promising cytokines and biomarkers have been identified for preventing osteosarcoma metastasis or improving therapeutic outcomes [7]. The detailed pathological mechanisms and the ideal treatment method for osteosarcoma are not fully understood
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