title: Adipose Stromal Cells from Visceral and Subcutaneous Fat Facilitate Migration of Ovarian Cancer Cells via IL-6/JAK2/STAT3 Pathway.
abstract: OBJECTIVE
  Adipose stromal cells (ASCs) play an important regulatory role in cancer progression and metastasis by regulating systemic inflammation and tissue metabolism. This study examined whether visceral and subcutaneous ASCs (V- and S-ASCs) facilitate the growth and migration of ovarian cancer cells.
  
  
  METHODS
  CD45-and CD31-double-negative ASCs were isolated from the subcutaneous and visceral fat using magnetic-activated cell sorting. Ovarian cancer cells were cultured in conditioned media (CM) obtained from ASCs to determine the cancer-promoting effects of ASCs. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, Boyden chamber assay, and western blotting were performed to determine the proliferative activity, migration ability, and activation of the JAK2/STAT3 pathway, respectively.
  
  
  RESULTS
  CM from ASCs enhanced the migration of the ovarian cancer line, SKOV3, via activation of the JAK2/STAT3 signaling pathway. Interestingly, in response to ASC-CM, the ascites cells derived from an ovarian cancer patient showed an increase in growth and migration. The migration of ovarian cancer cells was suppressed by blocking the activation of JAK2 and STAT3 using a neutralizing antibody against interleukin 6, small molecular inhibitors (e.g., WP1066 and TG101348), and silencing of STAT3 using siRNA. Anatomical differences between S- and V-ASCs did not affect the growth and migration of the ovarian cancer cell line and ascites cells from the ovarian cancer patients.
  
  
  CONCLUSIONS
  ASCs may regulate the progression of ovarian cancer, and possibly provide a potential target for anticancer therapy.
authors.affiliation: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.|Nano System Institute, Seoul National University, Seoul, Korea.
authors.forename: Boyun
authors.initials: B
authors.lastname: Kim
authors.affiliation: Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Hee Seung
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Soochi
authors.initials: S
authors.lastname: Kim
authors.affiliation: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Guy
authors.initials: G
authors.lastname: Haegeman
authors.affiliation: Departments of Obstetrics & Gynecology and Cellular & Molecular Medicine, Interdisciplinary School of Health Sciences, University of Ottawa, and Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
authors.forename: Benjamin K
authors.initials: BK
authors.lastname: Tsang
authors.affiliation: Peggy and Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Danny N
authors.initials: DN
authors.lastname: Dhanasekaran
authors.affiliation: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.|Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea.|WCU Biomodulation, Department of Agricultural Biotechnology, Seoul National University, Seoul, Korea.
authors.forename: Yong Sang
authors.initials: YS
authors.lastname: Song
mesh_terms: D050153:Abdominal Fat / Q000166:cytology*; D015415:Biomarkers; D002450:Cell Communication; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D015850:Interleukin-6 / Q000378:metabolism*; D053614:Janus Kinase 2 / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D011725:Pyridines / Q000494:pharmacology; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism*; D020032:Tyrphostins / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D011725:Pyridines; D050796:STAT3 Transcription Factor; D020032:Tyrphostins; C519885:WP1066; C507924:JAK2 protein, human; D053614:Janus Kinase 2
keywords: Adipose stromal cells; Adipose tissue; Cell movement; Interleukin-6; Ovarian neoplasms