RRC ID 63397
Author Cheng XB, Kohi S, Koga A, Hirata K, Sato N.
Title Hyaluronan stimulates pancreatic cancer cell motility.
Journal Oncotarget
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.
Volume 7(4)
Pages 4829-40
Published 2016-1-26
DOI 10.18632/oncotarget.6617
PII 6617
PMID 26684359
PMC PMC4826246
MeSH Adjuvants, Immunologic / pharmacology Apoptosis / drug effects Blotting, Western Carcinoma, Pancreatic Ductal / drug therapy Carcinoma, Pancreatic Ductal / metabolism Carcinoma, Pancreatic Ductal / pathology* Cell Movement / drug effects* Cell Proliferation / drug effects Coculture Techniques Fibroblasts / drug effects Fibroblasts / metabolism Fibroblasts / pathology Gene Expression Regulation, Neoplastic / drug effects* Glucuronosyltransferase / genetics Glucuronosyltransferase / metabolism* Humans Hyaluronan Synthases Hyaluronic Acid / pharmacology* Pancreatic Neoplasms / drug therapy Pancreatic Neoplasms / metabolism Pancreatic Neoplasms / pathology* RNA, Messenger / genetics Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction Stromal Cells / drug effects Stromal Cells / metabolism Stromal Cells / pathology Tumor Cells, Cultured Wound Healing
IF 5.168
Human and Animal Cells NOR-P1(RCB2139)