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Secretion of transforming growth factor-beta 1 and -beta 2 by malignant glioma cells
A Sasaki1, H Naganuma, E Satoh
1Department of Neurosurgery, Yamanashi Medical University.
Abstract:
The secretion of transforming growth factor-beta (TGF-beta), a growth inhibitory factor with immunosuppressive properties, was investigated in one glioblastoma cell line and seven surgically resected malignant glioma cells. Cultured cells from surgically resected tumors were examined immunohistochemically for glial fibrillary acidic protein (GFAP) and S-100 protein. The levels of TGF-beta 1 and TGF-beta 2 in culture supernatants from malignant glioma cells were determined by a specific bioassay using anti-TGF-beta 1 and anti-TGF-beta 2 antibodies. Two glioblastoma cell lines were cultured in the presence of TGF-beta 1 or TGF-beta 2 to assess the effect of TGF-beta on the growth of glioblastoma cells. Cultured cells from surgically resected tumors were positive for both GFAP and S-100 protein. Both active and latent forms of TGF-beta 1 and TGF-beta 2 were detected in the culture supernatants from malignant gliomas, except in one patient with anaplastic astrocytoma which secreted only latent forms of TGF-beta 1 and TGF-beta 2. There was no statistical difference in the levels of TGF-beta 1 and TGF-beta 2 in glioblastomas and anaplastic astrocytomas. Neither TGF-beta 1 nor TGF-beta 2 affected the growth of glioblastoma cells. These findings suggest that most malignant glioma cells secrete both TGF-beta 1 and TGF-beta 2, can convert TGF-beta from a latent to active form, and may suppress cytokine secretion by activated lymphocytes in vivo as well as in vitro.
Insights
Malignant glioma cells secrete transforming growth factor-beta (TGF-beta) 1 and 2. These cells can activate TGF-beta and may suppress immune responses, but TGF-beta does not impact glioma cell growth.
Area of Science:
- Neuro-oncology
- Immunology
- Cell Biology
Background:
- Transforming growth factor-beta (TGF-beta) is a key immunosuppressive and growth-inhibitory factor.
- Glioblastoma and malignant gliomas are aggressive brain tumors with complex cellular interactions.
Purpose of the Study:
- To investigate the secretion of TGF-beta 1 and TGF-beta 2 by malignant glioma cells.
- To determine the effect of TGF-beta on glioblastoma cell proliferation.
- To explore the potential of glioma cells to modulate TGF-beta activity.
Main Methods:
- Immunohistochemical analysis of glial fibrillary acidic protein (GFAP) and S-100 protein in tumor cells.
- Bioassay measurement of active and latent TGF-beta 1 and TGF-beta 2 in cell culture supernatants.
- In vitro culture of glioblastoma cells with TGF-beta 1 or TGF-beta 2.
Main Results:
- Malignant glioma cells express GFAP and S-100 protein.
- Both active and latent forms of TGF-beta 1 and TGF-beta 2 were detected in most malignant glioma supernatants.
- TGF-beta 1 and TGF-beta 2 did not significantly affect the growth of glioblastoma cells.
Conclusions:
- Malignant glioma cells are a source of TGF-beta 1 and TGF-beta 2.
- Glioma cells possess the capacity to convert latent TGF-beta to its active form.
- Secreted TGF-beta by gliomas may contribute to local immunosuppression in the tumor microenvironment.