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

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.

Niclosamide Suppresses Migration and Invasion of Human Osteosarcoma Cells by Repressing TGFBI Expression via the ERK Signaling Pathway

“…In osteosarcoma, Chen et al, reported that c-Met Inhibitor suppresses osteosarcoma progression via the ERK1/2 pathway [ 34 ]. In addition, Liu et al demonstrated that monocyte chemoattractant protein-1 regulates cell mobility via ERK/AP-1 pathway in osteosarcoma cells [ 35 ]. However, inhibiting ERK pathway could imply that other processes may be repressed.…”

Microbiota and the Immune System—Actors in the Gastric Cancer Story

“…The literature data also show that there is an increased risk of developing GC after gastric surgery [ 55 ]. The time lag between initial gastric surgery for mild disease and the development of gastric stump cancer is around 30 years or more, compared with 12 years if surgery was performed due to earlier detection of GC lesions [ 56 ].…”

MCP‑1 targeting: Shutting off an engine for tumor development (Review)

“…MCP-1 also induces Akt activation in a dose-dependent manner (46). In addition to the activation of the PI3K/Akt/mTOR signaling pathway, the c-Raf/MEK/ERK and MAPK signaling pathways play a role in MCP-1-induced tumor migration (47). Furthermore, the IP3-dependent Akt/PKB signaling pathway is associated with MCP-1-induced tumor proliferation and migration (48).…”

“…MCP-1 enhances the aggressiveness of NSCLC cells by increasing the level of MMP-9 expression in vitro (50). MCP-1 induces MMP production by activating the ERK1/2 and p38 MAPK signaling pathways, and upregulates MMP by activating c-Raf/Raf-1, MEK, ERK, MAPK, c-Jun, NF-κB and AP-1 (47,51,52). MMP cleaves cell-to-cell and cell-extracellular matrix adhesion components, which promotes cell detachment and leads to epithelial-mesenchymal transition (EMT) and enhances metastasis (53).…”