Increased chemotactic migration and growth in heparanase-overexpressing human U251n glioma cells.
Heparanase is an endoglycosidase that degrades heparan sulfate, the main polysaccharide constituent of the extracellular matrix (ECM) and basement membrane. Expression of the heparanase gene is associated with the invasion and metastatic potential of a variety of tumor-derived cell types. However, the roles of heparanase in the regulation of gene expression and the subsequent cell function changes other than invasion are not clear. In the current study, we overexpressed the human heparanase gene in a human U251n glioma cell line. We found that heparanase-overexpression significantly increased cell invasion, proliferation, anchorage-independent colony formation and chemotactic migration towards fetal bovine serum (FBS)-supplied medium and stromal cell-derived factor-1 (SDF-1). These phenotypic appearances were accompanied by enhanced protein kinase B (AKT) phosphorylation. Focal adhesion kinase (FAK) and extracellular signal-regulated kinase 1 (ERK1) signaling were not altered by heparanase-overexpression. These results indicate that heparanase has pleiotropic effects on tumor cells.
Hong
Xin
X
Department of Neurology, Henry Ford Health Science Center, Detroit, MI, USA. nsxin@neuro.hfh.edu
Jiang
Feng
F
Kalkanis
Steven N
SN
Zhang
Zheng Gang
ZG
Zhang
Xuepeng
X
Zheng
Xuguang
X
Jiang
Hao
H
Mikkelsen
Tom
T
Chopp
Michael
M
D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002633:Chemotaxis; D005109:Extracellular Matrix / Q000201:enzymology / Q000378:metabolism; D005910:Glioma / Q000201:enzymology* / Q000473:pathology; D005966:Glucuronidase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D014162:Transfection; D000099175:Heparanase
D005966:Glucuronidase; D051057:Proto-Oncogene Proteins c-akt; D000099175:Heparanase