title: Hyaluronan stimulates pancreatic cancer cell motility.
abstract: Hyaluronan (HA) accumulates in pancreatic ductal adenocarcinoma (PDAC), but functional significance of HA in the aggressive phenotype remains unknown. We used different models to investigate the effect of HA on PDAC cell motility by wound healing and transwell migration assay. Changes in cell motility were examined in 8 PDAC cell lines in response to inhibition of HA production by treatment with 4-methylumbelliferone (4-MU) and to promotion by treatment with 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or by co-culture with tumor-derived stromal fibroblasts. We also investigated changes in cell motility by adding exogenous HA. Additionally, mRNA expressions of hyaluronan synthases and hyaluronidases were examined using real time RT-PCR. Inhibition of HA by 4-MU significantly decreased the migration, whereas promotion of HA by TPA or co-culture with tumor-derived fibroblasts significantly increased the migration of PDAC cells. The changes in HA production by these treatments tended to be associated with changes in HAS3 mRNA expression. Furthermore, addition of exogenous HA, especially low-molecular-weight HA, significantly increased the migration of PDAC cells. These findings suggest that HA stimulates PDAC cell migration and thus represents an ideal therapeutic target to prevent invasion and metastasis.
authors.affiliation: Department of Surgery 1, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Fukuoka 807-8555, Japan.|Department of Breast Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning 110032, China.
authors.forename: Xiao-Bo
authors.initials: XB
authors.lastname: Cheng
authors.affiliation: Department of Surgery 1, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Fukuoka 807-8555, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Kohi
authors.affiliation: Department of Surgery 1, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Fukuoka 807-8555, Japan.
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Koga
authors.affiliation: Department of Surgery 1, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Fukuoka 807-8555, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Hirata
authors.affiliation: Department of Surgery 1, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Fukuoka 807-8555, Japan.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Sato
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D018920:Coculture Techniques; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured; D014945:Wound Healing
chemical_list: D000276:Adjuvants, Immunologic; D012333:RNA, Messenger; D006820:Hyaluronic Acid; D014453:Glucuronosyltransferase; D000076002:Hyaluronan Synthases
keywords: hyaluronan; hyaluronan synthase genes; hyaluronidase genes; migration; pancreatic cancer