Hyaluronan stimulates pancreatic cancer cell motility
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Xiao-Bo Cheng1,2, Shiro Kohi1, Atsuhiro Koga1, Keiji Hirata1, Norihiro Sato1
1Department of Surgery 1, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Fukuoka 807-8555, Japan
2Department of Breast Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning 110032, China
Norihiro Sato, e-mail: email@example.com
Keywords: hyaluronan, pancreatic cancer, migration, hyaluronan synthase genes, hyaluronidase genes
Received: September 01, 2015 Accepted: November 28, 2015 Published: December 14, 2015
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.
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