TRANSFORMING GROWTH FACTOR-BETA-1, FACTOR-BETA-2, AND FACTOR-BETA-3 SECRETED BY A HUMAN GLIOBLASTOMA CELL-LINE - IDENTIFICATION OF SMALL AND DIFFERENT FORMS OF LARGE LATENT COMPLEXES

Transforming growth factor-beta1 (TGF-beta1) has been found to occur as latent high molecular weight complexes, with or without an associated component denoted latent TGF-beta1-binding protein (LTBP). We show here that a human glioblastoma cell line (U-1240 MG) secretes all isoforms of TGF-betas found in mammalian cells (TGF-beta1, -beta2, and -beta3). Approximately 26% of the secreted TGF-beta is in an active form. Latent TGF-betas 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-beta1 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.