title: Chemokine CCL2 enhances survival and invasiveness of endometrial stromal cells in an autocrine manner by activating Akt and MAPK/Erk1/2 signal pathway.
abstract: OBJECTIVE
  To clarify the role and mechanism of CCL2 in regulating the biological functions of endometrial stromal cells (ESCs).
  
  
  METHODS
  The CCL2 effect on the viability, proliferation, and invasion in the eutopic ESCs from endometriosis.
  
  
  METHODS
  Research laboratories.
  
  
  METHODS
  Patients with endometriosis aged 23-47 years.
  
  
  METHODS
  None.
  
  
  METHODS
  Signal transduction and downstream molecules from CCR2.
  
  
  RESULTS
  We have found that the secretion of CCL2 by the eutopic ESCs from endometriosis is higher than that of healthy ESCs without endometriosis. The CCL2 can enhance the viability, proliferation, and invasion of ESCs in a dosage and time-dependent manner. Anti-CCL2 neutralizing antibody and CCR2 antagonist can completely abolish the increase in viability, proliferation, and invasiveness of ESCs induced by CCL2. The CCL2 can increase the expression of proliferating cell nuclear antigen, survivin, and matrix metalloproteinase 2, and decrease the expression of tissue inhibitor of metalloproteinase 1 and 2, and promote the viability, proliferation and invasiveness of ESCs by activating Akt and MAPK/Erk1/2 signal pathway, but not p38 and JNK signal pathway.
  
  
  CONCLUSIONS
  CCL2 might play an important role in regulating the functions of ESCs through Akt and MAPK/Erk1/2 signal pathway, and overexpression of CCL2 in ESCs and peritoneal fluid (PF) would lead to onset and development of endometriosis.
authors.affiliation: Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics & Gynecology, Fudan University Shanghai Medical College, Shanghai, People's Republic of China.
authors.forename: Ming-Qing
authors.initials: MQ
authors.lastname: Li
authors.forename: Hua-Ping
authors.initials: HP
authors.lastname: Li
authors.forename: Yu-Han
authors.initials: YH
authors.lastname: Meng
authors.forename: Xiao-Qiu
authors.initials: XQ
authors.lastname: Wang
authors.forename: Xiao-Yong
authors.initials: XY
authors.lastname: Zhu
authors.forename: Jie
authors.initials: J
authors.lastname: Mei
authors.forename: Da-Jin
authors.initials: DJ
authors.lastname: Li
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D019898:Autocrine Communication; D016022:Case-Control Studies; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004715:Endometriosis / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D004717:Endometrium / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction; D017154:Stromal Cells / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D000077022:Survivin; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D055815:Young Adult
chemical_list: C107489:BIRC5 protein, human; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D051034:Inhibitor of Apoptosis Proteins; D018809:Proliferating Cell Nuclear Antigen; D047428:Protein Kinase Inhibitors; D000077022:Survivin; C560822:TIMP1 protein, human; C560823:TIMP2 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D051057:Proto-Oncogene Proteins c-akt; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2