bFGF induces changes in hyaluronan synthase and hyaluronidase isoform expression and modulates the migration capacity of fibrosarcoma cells

被引:33
作者
Berdiaki, Aikaterini [1 ]
Nikitovic, Dragana [1 ]
Tsatsakis, Aristeidis [1 ]
Katonis, Pavlos [2 ]
Karamanos, Nikos K. [3 ]
Tzanakakis, George N. [1 ]
机构
[1] Univ Crete, Dept Histol, Div Morphol, Sch Med, Iraklion 71110, Greece
[2] Univ Hosp Heraklion, Dept Orthoped, Iraklion 71003, Greece
[3] Univ Patras, Dept Chem, Biochem Lab, GR-26110 Patras, Greece
来源
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS | 2009年 / 1790卷 / 10期
关键词
Fibrosarcoma; Hyaluronan; Basic fibroblast growth factor; Hyaluronan synthase; Hyaluronidase; HYAL1; HYALURONIDASE; BINDING PROTEINS; PROSTATE-CANCER; BREAST-CANCER; CD44; CLEAVAGE; TUMOR-CELLS; GROWTH; FIBROBLASTS; RECEPTORS; MOLECULE;
D O I
10.1016/j.bbagen.2009.06.013
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Background: Hyaluronan (HA) a glycosaminoglycan, is capable of transmitting extracellular matrix derived signals to regulate cellular functions. In this study, we investigated whether the changes in HT1080 and B6FS fibrosarcoma cell lines HA metabolism induced by basic fibroblast growth factor (bFGF) are correlated to their migration. Methods: Real-time PCR, in vitro wound healing assay, siRNA transfection, enzyme digestions, western blotting and immunofluorescence were utilized. Results: bFGF inhibited the degradation of HA by decreasing hyaluronidase-2 expression in HT1080 cells (p = 0.0028), increased HA-synthase-1 and -2 expression as we previously found and enhanced high molecular weight HA deposition in the pericellular matrix. Increased endogenous HA production (p = 0.0022) and treatment with exogenous high molecular weight HA (p = 0.0268) correlated with a significant decrease of HT1080 cell migration capacity. Transfection with siHAS2 and siHAS1 showed that mainly HAS1 synthesized high molecular weight HA regulates HT1080 cell motility. Induced degradation of the HA content by hyaluronidase treatment and addition of low molecular weight HA, resulted in a significant stimulation of HT1080 cells' motility (p<0.01). In contrast, no effects on B6FS fibrosarcoma cell motility were observed. Conclusions: bFGF regulates, in a cell-specific manner the migration capability of fibrosarcoma cells by modulating their HA metabolism. HA metabolism is suggested to be a potential therapeutic target in fibrosarcoma. (C) 2009 Elsevier B.V. All rights reserved.
引用
收藏
页码:1258 / 1265
页数:8
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