title: Adipocytes enhance the proliferation of human leiomyoma cells via TNF-α proinflammatory cytokine.
abstract: OBJECTIVE
  Obesity is a well-documented risk factor for uterine leiomyoma with a major impact on women health and health care system of the nation. Obesity is associated with increased secretion of adipokines that significantly influence growth and proliferation of tumor stroma and malignant cells. Adipokines, such as tumor necrosis factor α (TNF-α), are produced in the adipose tissue with concomitant expression in other organs and tissues. Increased and sustained cytokine production is associated with alterations in cell growth and differentiation. We, therefore, explored the influence of human adipocytes (SW872 cells)-mediated biological humoral factors on human uterine leiomyoma (HuLM) cells.
  
  
  METHODS
  We measured cell proliferation and expression of cell-proliferating proteins (proliferating cell nuclear antigen [PCNA], cyclin D1, and B-cell lymphoma 2 [BCL-2]) in human leiomyoma cells cocultured with SW872 cells. SW872-conditioned media was neutralized for TNF-α and proliferation of HuLM cells was observed along with antiapoptotic marker, BCL-2, using Western immunoblot.
  
  
  RESULTS
  We found that both SW872-conditioned media and coculture with SW872 cells increased HuLM cell proliferation significantly (P < .05). We determined that this effect was associated with the upregulation of specific markers for proliferation, such as PCNA, cyclin D1, and BCL-2 (P < .05). Furthermore, the addition of neutralizing antibodies, anti-TNF-α, to SW872-conditioned media reversed the proliferation of leiomyoma cells and induced apoptosis as indicated by the reduced expression of antiapoptotic marker BCL-2.
  
  
  CONCLUSIONS
  SW872 cells secrete TNF-α, which is associated with a proliferative gene profile in HuLM cells and may play a role in initiation and/or progression of uterine leiomyoma.
authors.affiliation: Department of Obstetrics and Gynecology, Center for Women's Health Research, Meharry Medical College, Nashville, TN 37208, USA.
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Nair
authors.forename: Ayman
authors.initials: A
authors.lastname: Al-Hendy
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000378:metabolism; D019938:Cyclin D1 / Q000378:metabolism; D005260:Female; D006801:Humans; D007889:Leiomyoma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D019899:Paracrine Communication / Q000187:drug effects; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014594:Uterine Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: D057134:Antibodies, Neutralizing; C530104:CCND1 protein, human; D017077:Culture Media, Conditioned; D018809:Proliferating Cell Nuclear Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D014409:Tumor Necrosis Factor-alpha; D019938:Cyclin D1
references.citation: Cell Commun Signal. 2010 Jun 10;8:10
references.pmid: 20537183
references.citation: Metabolism. 1999 Oct;48(10):1332-5
references.pmid: 10535400
references.citation: Oncology. 1999 Oct;57 Suppl 2:49-58
references.pmid: 10545803
references.citation: Eur J Cell Biol. 2001 Aug;80(8):554-61
references.pmid: 11561906
references.citation: Nutrition. 1991 Jul-Aug;7(4):251-5
references.pmid: 1802214
references.citation: J Endocrinol. 1993 Sep;138(3):517-28
references.pmid: 8277225
references.citation: J Biol Chem. 2001 Dec 28;276(52):48823-30
references.pmid: 11604390
references.citation: Arterioscler Thromb Vasc Biol. 2005 Oct;25(10):2062-8
references.pmid: 16123319
references.citation: J Clin Invest. 1995 May;95(5):2111-9
references.pmid: 7738178
references.citation: Eur J Cancer Prev. 2008 Jun;17(3):195-200
references.pmid: 18414189
references.citation: Science. 1993 Jan 1;259(5091):87-91
references.pmid: 7678183
references.citation: Obstet Gynecol. 1997 Dec;90(6):967-73
references.pmid: 9397113
references.citation: J Epidemiol. 1998 Aug;8(3):176-80
references.pmid: 9782674
references.citation: Cancer Lett. 2008 Aug 28;267(2):197-203
references.pmid: 18406516
references.citation: Oncogene. 2008 Oct 9;27(46):6068-74
references.pmid: 18574467
references.citation: Int J Obes Relat Metab Disord. 2004 Aug;28(8):993-7
references.pmid: 15211360
references.citation: Clin Obstet Gynecol. 2001 Jun;44(2):316-26
references.pmid: 11344995
references.citation: Int J Obes Relat Metab Disord. 2001 Oct;25(10):1407-15
references.pmid: 11673759
references.citation: Endocrinology. 2003 Sep;144(9):3765-73
references.pmid: 12933646
references.citation: Mol Med. 1997 Jan;3(1):37-48
references.pmid: 9132278
references.citation: Int J Med Sci. 2008 Aug 29;5(5):248-62
references.pmid: 18773088
references.citation: J Lipid Res. 1996 May;37(5):1162-6
references.pmid: 8725167
references.citation: Diabetes Care. 2004 Jan;27(1):47-52
references.pmid: 14693965
references.citation: Cancer Genet Cytogenet. 2006 Oct 1;170(1):71-5
references.pmid: 16965960
references.citation: J Biol Chem. 2001 Jul 13;276(28):26534-41
references.pmid: 11352921
references.citation: J Clin Invest. 1995 May;95(5):2409-15
references.pmid: 7738205
references.citation: Pflugers Arch. 2006 Jul;452(4):418-27
references.pmid: 16586095
references.citation: Eur Cytokine Netw. 1996 Apr-Jun;7(2):93-124
references.pmid: 8688493
references.citation: Best Pract Res Clin Obstet Gynaecol. 2008 Aug;22(4):589-601
references.pmid: 18373954
references.citation: Br J Nutr. 2004 Sep;92(3):347-55
references.pmid: 15469638
references.citation: Proc Soc Exp Biol Med. 1995 Sep;209(4):325-42
references.pmid: 7638240
references.citation: Br Med J (Clin Res Ed). 1986 Aug 9;293(6543):359-62
references.pmid: 3730804
references.citation: Curr Med Chem Cardiovasc Hematol Agents. 2004 Jul;2(3):197-208
references.pmid: 15320786
references.citation: Environ Health Perspect. 2003 Jun;111(8):1037-54
references.pmid: 12826476
references.citation: J Clin Endocrinol Metab. 1998 Mar;83(3):847-50
references.pmid: 9506738
references.citation: Fertil Steril. 2007 Aug;88(2):255-71
references.pmid: 17658523
references.citation: Clin Sci (Lond). 2008 Feb;114(4):275-88
references.pmid: 18194136
references.citation: Fertil Steril. 2002 Jul;78(1):1-12
references.pmid: 12095482
references.citation: Obstet Gynecol. 2005 Mar;105(3):563-8
references.pmid: 15738025
references.citation: J Clin Endocrinol Metab. 2004 Jun;89(6):2548-56
references.pmid: 15181022
references.citation: Proc Natl Acad Sci U S A. 2003 Jun 10;100(12):7265-70
references.pmid: 12756299
references.citation: J Clin Endocrinol Metab. 1998 Aug;83(8):2907-10
references.pmid: 9709967