Human glioblastoma cell derived transforming growth factor-beta 2: evidence for secretion of both high and low molecular weight biologically active forms.
Transforming growth factors beta (TGF-beta) form a family of multifunctional polypeptides which in the active dimeric forms have a molecular weight of 25 kDa. Human glioblastoma cells secrete immunosuppressive TGF-beta consisting mostly of TGF-beta 2 rather than TGF-beta 1. The results shown here demonstrate that in addition to the mature 25 kDa form of TGF-beta 2, glioblastoma cells release a biologically active high molecular weight form of TGF-beta 2 which suppresses the interleukin-2-dependent growth of a T helper cell line. The high and low molecular weight forms of TGF-beta 2, separated by polyacrylamide gel electrophoresis under non-reducing conditions, can be eluted from the gel retaining their immunosuppressive activity. Similar results were obtained when analyzing supernatants of Chinese hamster ovary (CHO) cells transfected with a cDNA for TGF-beta 2. Both the high molecular weight form (90-120 kDa) and the 25 kDa form can be immunoprecipitated with a monoclonal antibody against mature native TGF-beta 2 and are detectable in tumor cyst fluid from glioblastoma patients. Taken together, the data provide evidence that in addition to the well-characterized 25 kDa form of TGF-beta 2 glioblastoma cells also secrete a high molecular weight form (90-120 kDa) with the biological characteristics of TGF-beta 2.
Bodmer
S
S
Department of Internal Medicine, University Hospital of Zurich, Switzerland.
Huber
D
D
Heid
I
I
Fontana
A
A
D000818:Animals; D001826:Body Fluids / Q000378:metabolism; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D003560:Cysts / Q000378:metabolism; D004247:DNA; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000378:metabolism; D008233:Lymphotoxin-alpha / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D008970:Molecular Weight; D010053:Ovary / Q000166:cytology / Q000378:metabolism; D011233:Precipitin Tests; D014162:Transfection; D014407:Tumor Cells, Cultured
D007166:Immunosuppressive Agents; D008233:Lymphotoxin-alpha; D004247:DNA