Monocyte Chemoattractant Protein-1 promotes cancer cell migration via c-Raf/MAPK/AP-1 pathway and MMP-9 production in os
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(2020) 39:254
RESEARCH
Open Access
Monocyte Chemoattractant Protein-1 promotes cancer cell migration via c-Raf/ MAPK/AP-1 pathway and MMP-9 production in osteosarcoma Ju-Fang Liu1, Po-Chun Chen2,3,4, Tsung-Ming Chang5 and Chun-Han Hou6*
Abstract Background: Osteosarcoma 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. Methods: The osteosarcoma cell migratory ability was assessed by transwell migration assay. The MCP-1 and MMP9 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. Results: The 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. Conclusions: Our results provide prognostic value of MCP-1 in osteosarcoma by promoting MMP-9 expression. Keywords: Osteosarcoma, MCP-1, Migration, MMP-9
Background 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]. High-grade osteosarcoma represents the development of metastasis, mainly in the lungs * Correspondence: [email protected] 6 Department of Orthopedic Surgery, National Taiwan University Hospital, 100, NO. 1, Jen-Ai Road, Taipei City 11102, Taiwan, ROC Full list of author information is available at the end of the article
[3]. Osteosarcoma metastasis also occurs in organs such as the bones and lymph nodes [4]. Pulmonary metastasis can be observed in approximately 15–20% of the patients at initial diagnosis and in 40% of the patients at a later follow-up [5]. 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]. However, the detailed pathological mechanisms and the ideal treatment method for osteosarcoma are not fully understood.
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