Immunosuppression and transforming growth factor-beta in glioblastoma. Preferential production of transforming growth factor-beta 2.
Transforming growth factor (TGF)-beta 1 is a polypeptide that is assumed to play a fundamental role in the growth of both normal and neoplastic cells. TGF-beta 2 is a closely related polypeptide, originally described as glioblastoma cell-derived T cell suppressor factor (G-TsF) due to its immunosuppressive activity. Expression of the genes for TGF-beta 1 and G-TsF/TGF-beta 2 was examined in tumor cells and was found to be different in several cell lines and tissues that were tested. Whereas two glioblastoma cell lines expressed both TGF-beta 1 and G-TsF/TGF-beta 2 mRNA, one melanoma and neuroblastoma cell lines showed only TGF-beta 1 mRNA which in the case of the neuroblastoma required cycloheximide treatment for its detection. The coordinate expression of the genes for TGF-beta 1 and G-TsF/TGF-beta 2 in glioblastoma was not paralleled by secretion of both polypeptides as only G-TsF/TGF-beta 2 but not TGF-beta 1 was identified in supernatants of glioblastoma cells. These data provide evidence for a post-transcriptional level of regulation for production of the two forms of TGF-beta. As mRNA for G-TsF/TGF-beta 2 was also identified in fresh surgically removed human glioblastoma tissue, G-TsF/TGF-beta 2 may also be secreted within the tumor in vivo. Unlike glioblastoma, human fetal brain tissues or adult brain specimens studied did not express detectable levels of TGF-beta mRNA. Impaired cell-mediated immunity is an established finding in patients with glioblastoma. Secretion of G-TsF/TGF-beta 2 by tumor cells in vivo may contribute to decreased immune surveillance for tumor development, as well as neovascularization of the tumor tissue.
Bodmer
S
S
Department of Internal Medicine, University Hospital, Zürich, Switzerland.
Strommer
K
K
Frei
K
K
Siepl
C
C
de Tribolet
N
N
Heid
I
I
Fontana
A
A
D000328:Adult; D000818:Animals; D001483:Base Sequence; D001932:Brain Neoplasms / Q000032:analysis / Q000276:immunology; D002460:Cell Line; D002474:Cell-Free System; D005260:Female; D005786:Gene Expression Regulation; D005910:Glioma / Q000032:analysis / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D008875:Middle Aged; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000096:biosynthesis; D012333:RNA, Messenger / Q000302:isolation & purification; D013491:Suppressor Factors, Immunologic / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology; D015291:Transforming Growth Factors / Q000096:biosynthesis* / Q000235:genetics; D014407:Tumor Cells, Cultured
D009363:Neoplasm Proteins; D012333:RNA, Messenger; D013491:Suppressor Factors, Immunologic; D015291:Transforming Growth Factors