title: Unfractionated Heparin Selectively Modulates the Expression of CXCL8, CCL2 and CCL5 in Endometrial Carcinoma Cells.
abstract: OBJECTIVE
  This in vitro study analyzed the impact of heparins on expression of chemokines in human endometrial adenocarcinoma cell lines.
  
  
  METHODS
  Cell lines were incubated with unfractionated heparin (UFH), low molecular weight heparins (LMWH) and fondparinux under hypoxic and normoxic conditions. Chemokine (C-X-C motif) ligand 8 (CXCL8), CC-chemokine ligand 2 (CCL2) and CCL5 were detected by enzyme-linked immunosorbent assays and real-time reverse transcriptase-polymerase chain reaction and cell viability by fluorometric assay.
  
  
  RESULTS
  Different adenocarcinoma cell lines had distinct patterns of chemokine expression. UFH attenuated the secretion of CXCL8 and CCL2, and enhanced that of CCL5. The observed effects of heparin were in addition to the anti-coagulatory properties of heparin and dependent on molecular size and charge.
  
  
  CONCLUSIONS
  UFH has selective modulating effects on the secretion of CXCL8, CCL2 and CCL5 in different endometrial adenocarcinoma cell lines. Molecular size and charge are relevant for these observed effects. By influencing the expression of these inflammatory mediators and thereby affecting the tumour microenvironment, heparins and related agents might play an essential role in the development of new therapeutic strategies.
authors.affiliation: Department of Obstetrics and Gynecology, University Hospital of Heidelberg, Heidelberg, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Doster
authors.affiliation: Department of Obstetrics and Gynecology, University of Greifswald, Greifswald, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Schwarzig
authors.affiliation: Department of Obstetrics and Gynecology, University of Greifswald, Greifswald, Germany.
authors.forename: Marek
authors.initials: M
authors.lastname: Zygmunt
authors.affiliation: Department of Obstetrics and Gynecology, University Hospital of Heidelberg, Heidelberg, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Rom
authors.affiliation: Department of Obstetrics and Gynecology, University Hospital of Heidelberg, Heidelberg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Schütz
authors.affiliation: Department of Obstetrics and Gynecology, University Hospital of Heidelberg, Heidelberg, Germany herbert.fluhr@med.uni-heidelberg.de.
authors.forename: Herbert
authors.initials: H
authors.lastname: Fluhr
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism*; D045744:Cell Line, Tumor; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000378:metabolism*; D005260:Female; D000077425:Fondaparinux; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D011134:Polysaccharides / Q000494:pharmacology
chemical_list: C111835:CCL2 protein, human; C483024:CCL5 protein, human; C508606:CXCL8 protein, human; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D016209:Interleukin-8; D011134:Polysaccharides; D006493:Heparin; D000077425:Fondaparinux
keywords: Heparin; chemokines; endometrial adenocarcinoma; tumour environment