title: Overexpression of chloride channel-3 is associated with the increased migration and invasion ability of ectopic endometrial cells from patients with endometriosis.
abstract: OBJECTIVE
  Is chloride channel-3 (ClC-3) involved in regulating the biological behavior of endometrial stromal cells (ESCs)?
  
  
  CONCLUSIONS
  ClC-3 promotes endometriotic cell migration and invasion.
  
  
  BACKGROUND
  ClC-3 plays a significant role in the migration and invasion of various kinds of cells.
  
  
  METHODS
  An ITALIC! in vitro investigation of the effect of ClC-3 on the migration and invasion of ectopic ESCs from patients with endometriosis.
  
  
  METHODS
  The ectopic and eutopic endometrial samples from 43 female patients with endometriosis and the endometrial samples from 39 non-endometriotic female patients were collected. Primary cells from these samples were isolated and cultured. Real-time RT-PCR, immunohistochemistry and western blot were used to detect the expression of ClC-3 and matrix metalloproteinase 9 (MMP-9). Small interfering RNA (siRNA) technology was employed to knock down ClC-3 expression. The migration and invasion ability of ESCs was measured by the transwell assay with uncoated or Matrigel-coated membranes.
  
  
  RESULTS
  The expression of ClC-3 mRNA and proteins was significantly up-regulated in the ectopic tissues from endometriotic patients, while that in the eutopic endometrial tissues of the same patients did not significantly differ from that in non-endometriotic patients. The migration and invasion ability and MMP-9 expression was increased in the ESCs from ectopic endometrial tissues. The knockdown of ClC-3 expression by ClC-3 siRNA inhibited ESC migration and invasion and attenuated the expression of MMP-9. ClC-3 expression level was well-correlated to the clinical characteristics and symptoms of endometriosis patients, including infertility, dysmenorrhea, chronic pelvic pain, dyspareunia and diameter of endometriosis lesion.
  
  
  CONCLUSIONS
  Further studies are needed to examine the regulatory mechanism of estrogen on ClC-3 expression of ESCs.
  
  
  CONCLUSIONS
  ClC-3 is involved in the migration and invasion processes of ESCs and can regulate MMP-9 expression. Up-regulation of ClC-3 expression may contribute to endometriosis development by regulating MMP-9 expression.
  
  
  BACKGROUND
  This work was supported by the National Natural Science Foundation of China (81173064, 81272223, 81273539), the Ministry of Education of China (20124401110009), the Natural Science Foundation of Guangdong Province (S2011010001589) and the Science and Technology Programs of Guangdong (2013B051000059), Guangzhou (2013J500015) and Dongguan (2011108102006). The authors have no conflict of interest.
authors.affiliation: Department of Pharmacology, Medical College, Jinan University, Guangzhou 510632, China Department of Pathophysiology, Medical College, Jinan University, Guangzhou, China.
authors.forename: Yu-tao
authors.initials: YT
authors.lastname: Guan
authors.affiliation: Department of Obstetrics and Gynecology, Guangzhou Women and Children's Medical Center, Guangzhou, China.
authors.forename: Yan-qing
authors.initials: YQ
authors.lastname: Huang
authors.affiliation: Department of Pharmacology, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Jia-bao
authors.initials: JB
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, Medical College, Jinan University, Guangzhou 510632, China Department of Pathophysiology, Medical College, Jinan University, Guangzhou, China.
authors.forename: Zhi-qin
authors.initials: ZQ
authors.lastname: Deng
authors.affiliation: Department of Physiology, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Physiology, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Zhou-yi
authors.initials: ZY
authors.lastname: Lai
authors.affiliation: Department of Pharmacology, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Hai-bo
authors.initials: HB
authors.lastname: Wang
authors.affiliation: Department of Physiology, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Xiao-xue
authors.initials: XX
authors.lastname: Sun
authors.affiliation: Department of Obstetrics and Gynecology, Guangzhou Women and Children's Medical Center, Guangzhou, China.
authors.forename: Ya-li
authors.initials: YL
authors.lastname: Zhu
authors.affiliation: Department of Obstetrics and Gynecology, Guangzhou Women and Children's Medical Center, Guangzhou, China.
authors.forename: Miao-miao
authors.initials: MM
authors.lastname: Du
authors.affiliation: Department of Pharmacology, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Lin-yan
authors.initials: LY
authors.lastname: Zhu
authors.affiliation: Department of Pharmacology, Medical College, Jinan University, Guangzhou 510632, China Department of Pathophysiology, Medical College, Jinan University, Guangzhou, China tchenlixin@jnu.edu.cn twangliwei@jnu.edu.cn.
authors.forename: Li-xin
authors.initials: LX
authors.lastname: Chen
authors.affiliation: Department of Pathophysiology, Medical College, Jinan University, Guangzhou, China Department of Physiology, Medical College, Jinan University, Guangzhou 510632, China tchenlixin@jnu.edu.cn twangliwei@jnu.edu.cn.
authors.forename: Li-wei
authors.initials: LW
authors.lastname: Wang
mesh_terms: D018929:Cell Culture Techniques; D002465:Cell Movement / Q000235:genetics*; D002478:Cells, Cultured; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004715:Endometriosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004717:Endometrium / Q000166:cytology / Q000378:metabolism; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D018118:Chloride Channels; C115376:ClC-3 channel; D020780:Matrix Metalloproteinase 9
keywords: CLCN3; ClC-3; endometriosis; invasion; migration