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Autocrine Production of PDGF Stimulated by the Tenascin-C-Derived Peptide TNIIIA2 Induces Hyper-Proliferation in Glioblastoma Cells.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2019 Jun 28; Vol. 20 (13). Date of Electronic Publication: 2019 Jun 28. - Publication Year :
- 2019
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Abstract
- Expression level of tenascin-C is closely correlated to poor prognosis in glioblastoma patients, while the substantial role of tenascin-C responsible for aggressive progression in glioblastoma cells has not been clarified. We previously found that peptide TNIIIA2, which is derived from the tumor-associated tenascin-C variants, has the ability to promote cell adhesion by activating β1-integrins. Our recent study demonstrated that potentiated activation of integrin α5β1 by TNIIIA2 causes not only a dysregulated proliferation in a platelet-derived growth factor (PDGF)-dependent manner, but also disseminative migration in glioblastoma cells. Here, we show that TNIIIA2 enhances the proliferation in glioblastoma cells expressing PDGF-receptorβ, even without exogenous PDGF. Mechanistically, TNIIIA2 induced upregulated expression of PDGF, which in turn stimulated the expression of tenascin-C, a parental molecule of TNIIIA2. Moreover, in glioblastoma cells and rat brain-derived fibroblasts, tenascin-C upregulated matrix metalloproteinase-2, which has the potential to release TNIIIA2 from tenascin-C. Thus, it was shown that autocrine production of PDGF triggered by TNIIIA2 functions to continuously generate a functional amount of PDGF through a positive spiral loop, which might contribute to hyper-proliferation in glioblastoma cells. TNIIIA2 also enhanced in vitro disseminative migration of glioblastoma cells via the PKCα signaling. Collectively, the tenascin-C/TNIIIA2 could be a potential therapeutic target for glioblastoma.
- Subjects :
- Animals
Brain Neoplasms pathology
Cell Line, Tumor
Cell Movement
Cells, Cultured
Fibroblasts metabolism
Fibroblasts physiology
Glioblastoma pathology
Humans
Male
Matrix Metalloproteinase 2 metabolism
Mice
Neurons drug effects
Neurons metabolism
Neurons physiology
Peptide Fragments chemistry
Peptide Fragments pharmacology
Rats
Rats, Wistar
Receptors, Platelet-Derived Growth Factor metabolism
Tenascin chemistry
Autocrine Communication
Brain Neoplasms metabolism
Cell Proliferation
Glioblastoma metabolism
Platelet-Derived Growth Factor metabolism
Tenascin metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 20
- Issue :
- 13
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 31261783
- Full Text :
- https://doi.org/10.3390/ijms20133183