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Hyaluronic Acid Induces Osteopontin via the
Phosphatidylinositol 3-Kinase/Akt Pathway to Enhance the Motility of Human
Glioma Cells
Kim MS, Park MJ, Moon EJ, Kim SJ, Lee CH, Yoo H, Shin SH, Song ES, Lee SH
Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi,
Korea.
Hyaluronic acid (HA) binds to cell-surface receptors such as CD44, and seems
to be involved in cell adhesion, motility, and tumor progression in brain.
To identify gene expression changes that are initiated by HA, we explored
human cytokine arrays in U87MG glioma cells and identified osteopontin, a
secreted matrix protein, as a transcriptional target of HA.
Interestingly,
expression of osteopontin was induced by HA in glioma cells lacking
functional PTEN, a tumor suppressor gene (U87MG, U251MG, and U373MG), but
not in wild-type (wt)-PTEN-harboring cells (LN18 and LN428).
To confirm the
role of PTEN, adenoviral (Ad)-wt-PTEN was used to induce ectopic expression
of wt-PTEN in U87MG cells, leading to reduced HA-mediated osteopontin
induction.
Reciprocally, transfection with dominant-negative Akt repressed
HA-induced osteopontin expression.
Furthermore, HA promoted the motility of
glioma cells, and down-regulation of induced osteopontin activity via a
neutralizing anti-osteopontin antibody repressed HA-induced motility in
vitro.
Together, these results strongly suggest that induction of
osteopontin expression by HA is dependent on activation of the
phosphatidylinositol 3-kinase/Akt pathway.
Furthermore, our data indicate
that PTEN can effectively modulate the expression of osteopontin, and
HA-induced osteopontin plays an important role in the motility response
induced by HA in human glioma cells.
PMID: 15705860 [PubMed - in process]
Source: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15705860
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