PMID- 33228783 OWN - NLM STAT- MEDLINE DCOM- 20210803 LR - 20210803 IS - 1756-9966 (Electronic) IS - 0392-9078 (Print) IS - 0392-9078 (Linking) VI - 39 IP - 1 DP - 2020 Nov 23 TI - Monocyte Chemoattractant Protein-1 promotes cancer cell migration via c-Raf/MAPK/AP-1 pathway and MMP-9 production in osteosarcoma. PG - 254 LID - 10.1186/s13046-020-01756-y [doi] LID - 254 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. FAU - Liu, Ju-Fang AU - Liu JF AD - School of Oral Hygiene, College of Oral Medicine, Taipei Medical University, Taipei, 110, Taiwan. FAU - Chen, Po-Chun AU - Chen PC AD - Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, 40447, Taiwan. AD - Translational medicine center, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei City, 11101, Taiwan. AD - Department of Biotechnology, College of Medical and Health Science, Asia University, Taichung, 41354, Taiwan. FAU - Chang, Tsung-Ming AU - Chang TM AD - School of Medicine, Institute of Physiology, National Yang-Ming University, Taipei City, 11221, Taiwan. FAU - Hou, Chun-Han AU - Hou CH AD - Department of Orthopedic Surgery, National Taiwan University Hospital, 100, NO. 1, Jen-Ai Road, Taipei City, 11102, Taiwan, ROC. chhou@ntu.edu.tw. LA - eng PT - Journal Article DEP - 20201123 PL - England TA - J Exp Clin Cancer Res JT - Journal of experimental & clinical cancer research : CR JID - 8308647 RN - 0 (CCL2 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Transcription Factor AP-1) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-raf) RN - EC 2.7.11.1 (Raf1 protein, human) RN - EC 2.7.11.24 (MAPK1 protein, human) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1) RN - EC 3.4.24.35 (MMP9 protein, human) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) SB - IM MH - Animals MH - Bone Neoplasms/*metabolism/pathology MH - Cell Line, Tumor MH - Cell Movement/physiology MH - Cell Proliferation/physiology MH - Chemokine CCL2/*metabolism MH - HEK293 Cells MH - Heterografts MH - Humans MH - MAP Kinase Signaling System MH - Male MH - Matrix Metalloproteinase 9/*metabolism MH - Mice MH - Mice, SCID MH - Mitogen-Activated Protein Kinase 1/*metabolism MH - Osteosarcoma/*metabolism/pathology MH - Prognosis MH - Proto-Oncogene Proteins c-raf/*metabolism MH - Transcription Factor AP-1/*metabolism MH - Transfection PMC - PMC7684958 OTO - NOTNLM OT - MCP-1 OT - MMP-9 OT - Migration OT - Osteosarcoma COIS- The authors state no conflict of interest. EDAT- 2020/11/25 06:00 MHDA- 2021/08/04 06:00 PMCR- 2020/11/23 CRDT- 2020/11/24 05:39 PHST- 2020/06/05 00:00 [received] PHST- 2020/10/30 00:00 [accepted] PHST- 2020/11/24 05:39 [entrez] PHST- 2020/11/25 06:00 [pubmed] PHST- 2021/08/04 06:00 [medline] PHST- 2020/11/23 00:00 [pmc-release] AID - 10.1186/s13046-020-01756-y [pii] AID - 1756 [pii] AID - 10.1186/s13046-020-01756-y [doi] PST - epublish SO - J Exp Clin Cancer Res. 2020 Nov 23;39(1):254. doi: 10.1186/s13046-020-01756-y.