TY - JOUR
T1 - Monocyte Chemoattractant Protein-1 promotes cancer cell migration via c-Raf/MAPK/AP-1 pathway and MMP-9 production in osteosarcoma
AU - Liu, Ju Fang
AU - Chen, Po Chun
AU - Chang, Tsung Ming
AU - Hou, Chun Han
N1 - Funding Information:
This study was supported by grants from the Ministry of Science and Technology, Taiwan, R.O.C. (MOST108–2314-B-002-211-MY3 and MOST106–2314-B-341-001-MY3), Shin-Kong Wu Ho-Su Memorial Hospital (SKH-8302-106-0402) and National Taiwan University Hospital (NTUH 108-S1405). We thank the staff of the Eighth Core Lab in the Department of Medical Research at National Taiwan University Hospital for their technical support during the study.
Publisher Copyright:
© 2020, The Author(s).
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/12
Y1 - 2020/12
N2 - 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.
AB - 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.
KW - MCP-1
KW - Migration
KW - MMP-9
KW - Osteosarcoma
UR - http://www.scopus.com/inward/record.url?scp=85096397024&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85096397024&partnerID=8YFLogxK
U2 - 10.1186/s13046-020-01756-y
DO - 10.1186/s13046-020-01756-y
M3 - Article
C2 - 33228783
AN - SCOPUS:85096397024
VL - 39
JO - Journal of Experimental and Clinical Cancer Research
JF - Journal of Experimental and Clinical Cancer Research
SN - 0392-9078
IS - 1
M1 - 254
ER -