Abstract
Transforming growth factor-beta 1 (TGF-beta 1) has been found to occur as latent high molecular weight complexes, with or without an associated component denoted latent TGF-beta 1-binding protein (LTBP). We show here that a human glioblastoma cell line (U-1240 MG) secretes all isoforms of TGF-beta s found in mammalian cells (TGF-beta 1, -beta 2, and -beta 3). Approximately 26% of the secreted TGF-beta is in an active form. Latent TGF-beta s were partially purified from medium conditioned by the U-1240 MG cell line using anion exchange chromatography. Analysis of the different fractions by immunoblotting using antisera against precursor parts of the different TGF-beta isoforms, and against LTBP, revealed that not only TGF-beta 1 but also other isoforms of TGF-beta may occur in high molecular weight forms containing LTBP. In addition, each one of the TGF-beta isoforms occurred in smaller forms not containing LTBP. Interestingly, each of the TGF-beta isoforms was also seen in complexes of about 210 kDa containing associated component(s) distinct from LTBP. These results indicate that each of the different isoforms of TGF-beta is synthesized and secreted by this glioblastoma cell line in several different high molecular weight latent forms; the biological importance of the various latent TGF-beta complexes is discussed.
Highlights
Found to occur as latent high molecular weight complexes, with or without an associated component denoted latent Transforming growth factor-81 (TGF-81)-binding protein (LTBP).We show here that a human glioblastoma cell line (U-1240 MG)
We show inthepresent communication that a human glioblastoma cell line, U-1240 MG, secretes all three known human isoforms of TGF-p.Eachone of thethreeTGF-p
-97 isoformsoccursin threedifferent high molecular weight forms, i.e. in large complexes containing @-LAPS covalently associatedwith latent TGF-81-binding protein (LTBP) or other not yet identified compocomplexes represent latent forms of the respective TGF-/3 molecules. This seems likely in view of the findings that most of the TGF-0 secretebdy U-1240 MG was in latent form and since this was the case for individual fractions of the Q-Sepharose chromatography (Table I and Fig. 2 0 )
Summary
Transforming growth factor-81 (TGF-81) has been latent TGF-P1complex is composed of three components,i.e. found to occur as latent high molecular weight complexes, with or without an associated component denoted latent TGF-81-binding protein (LTBP).We show here that a human glioblastoma cell line (U-1240 MG). These results indicate that each of the different isoforms of TGF-8 is synthesized and secreted by thisglioblastoma cellline in severaldifferenthigh molecular weight latent forms; the biological importance of the various latent TGF-8 complexes is discussed. The abbreviations used are: TGF-0, transforming growth factorp; LTBP,latentTGF-pl-bindingprotein;LAP,latency-associated peptide; EGF, epidermal growth factor; DMEM,Dulbecco’s modified of different isoforms of TGF-P in human glioma cell lines. We have identified large latent TGF-P complexes containing associated component(s) which are immunologically distinct from LTBP
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