Monocyte Chemoattractant Protein-1 promotes cancer cell migration via c-Raf/MAPK/AP-1 pathway and MMP-9 production in osteosarcoma

Ju Fang Liu, Po Chun Chen, Tsung Ming Chang, Chun Han Hou

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

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 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. 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.

Original languageEnglish
Article number254
JournalJournal of Experimental and Clinical Cancer Research
Volume39
Issue number1
DOIs
Publication statusPublished - Dec 2020

Keywords

  • MCP-1
  • Migration
  • MMP-9
  • Osteosarcoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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