title: Enoxaparin Attenuates Mouse Colon Cancer Liver Metastases by Inhibiting Heparanase and Interferon-γ-inducible Chemokines.
abstract: OBJECTIVE
  Low-molecular-weight heparin (LMWH) has been suggested to reduce the risk of cancer progression in both preclinical and clinical studies but the underlying mechanisms remain poorly explored. The aim of the study was to investigate the anti-metastatic role of enoxaparin, a clinically-used LMWH, in a murine model of colon cancer and to explore its underlying mechanisms.
  
  
  METHODS
  Using a reproducible mouse model of colon carcinomas, we assessed the capacity of enoxaparin, a LMWH, to affect tumor metastasis of colon carcinoma cell lines in mice.
  
  
  RESULTS
  The hepatic growth of colon carcinoma metastases was strongly inhibited by enoxaparin compared to (Ctrl) group (p=0.001). This effect was associated to an inhibition of heparanase mRNA expression and protein production both in vivo and in vitro. In addition, enoxaparin inhibited the liver and serum production of interferon gamma (Ifnγ)-inducible chemokine receptor ligands. Overexpression of heparanase prompted proliferation, migration and growth of colon carcinoma in vitro and in vivo to a point that was not affected by enoxaparin in vivo anymore.
  
  
  CONCLUSIONS
  Enoxaparin decreased liver metastases in a mouse model of colon carcinoma. These results suggest that enoxaparin may benefit patients with cancer and deserves further laboratory and clinical investigations.
authors.affiliation: Department of Surgery, Geneva University Hospitals, Faculty of Medicine, Geneva, Switzerland Souad.Djaafar@unige.ch.
authors.forename: Souad
authors.initials: S
authors.lastname: Djaafar
authors.affiliation: Division of Clinical Pathology, Geneva University Hospitals, Faculty of Medicine, Geneva, Switzerland.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Dunand-Sautier
authors.affiliation: Department of Surgery, Geneva University Hospitals, Faculty of Medicine, Geneva, Switzerland Hepato-Pancreato-Biliary Center, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Carmen
authors.initials: C
authors.lastname: Gonelle-Gispert
authors.affiliation: Department of Surgery, Geneva University Hospitals, Faculty of Medicine, Geneva, Switzerland.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Lacotte
authors.affiliation: Division of Clinical Pathology, Geneva University Hospitals, Faculty of Medicine, Geneva, Switzerland.
authors.forename: Ariane
authors.initials: A
authors.lastname: DE Agostini
authors.affiliation: Department of Surgery, Geneva University Hospitals, Faculty of Medicine, Geneva, Switzerland Hepato-Pancreato-Biliary Center, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Majno
authors.initials: M
authors.lastname: Petro
authors.affiliation: Division of Clinical Pathology, Geneva University Hospitals, Faculty of Medicine, Geneva, Switzerland.
authors.forename: Laura
authors.initials: L
authors.lastname: Rubbia-Brandt
authors.affiliation: Department of Surgery, Geneva University Hospitals, Faculty of Medicine, Geneva, Switzerland Hepato-Pancreato-Biliary Center, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Philippe
authors.initials: P
authors.lastname: Morel
authors.affiliation: Department of Surgery, Geneva University Hospitals, Faculty of Medicine, Geneva, Switzerland Hepato-Pancreato-Biliary Center, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Toso
authors.affiliation: Department of Surgery, Geneva University Hospitals, Faculty of Medicine, Geneva, Switzerland Hepato-Pancreato-Biliary Center, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Gilles
authors.initials: G
authors.lastname: Mentha
mesh_terms: D000818:Animals; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D004195:Disease Models, Animal; D017984:Enoxaparin / Q000008:administration & dosage*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005966:Glucuronidase / Q000037:antagonists & inhibitors; D006801:Humans; D007371:Interferon-gamma / Q000008:administration & dosage / Q000378:metabolism; D008024:Ligands; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000556:secondary; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D019707:Receptors, Chemokine / Q000096:biosynthesis; D000099175:Heparanase
chemical_list: D018925:Chemokines; D017984:Enoxaparin; D005966:Glucuronidase; D007371:Interferon-gamma; D008024:Ligands; D019707:Receptors, Chemokine; D000099175:Heparanase
keywords: Colorectal cancer (CRC); LMWH; chemokines; heparanase; metastasis