TGFβ1 and TGFβ2 are potential growth regulators for low‐grade and malignant gliomas in vitro: Evidence in support of an autocrine hypothesis

Low-grade astrocytomas, anaplastic astrocytomas and glio-blastomas in vitro were found to ubiquitously produce the mRNA of transforming growth factor-β (TGFβ). TGFβ1 and TGFβ2 mRNA were expressed to a lesser degree among the hyperdiploid malignant gliomas. By radioreceptor assay of conditioned medium, TGFβ was secreted predominantly in latent form, in both latent and active form, or only in active form within a panel of low-grade and malignant gliomas. The TGFβ receptor (types I, II and III) was evident among the glioma lines. Many near-diploid gliomas were growth-inhibited by TGFβ1 and TGFβ2. in vitro. Most hyperdiploid glioblastomas showed a positive mitogenic response to exogenous TGFβ1 and TGFβ2. A synergistic or additive mitogenic interaction with epidermal growth factor and insulin was observed among some. Under serum-free conditions, anti-TGFβ antibody neutralized the expected growth-regulatory effect of endogenous TGFβ1 thus establishing the specificity of the response in vitro. TGFβ1 also enhanced the clonogenicity of certain gliomas which had been growth-stimulated in monolayer. Thus, basic elements in support of an autocrine hypothesis have been demonstrated: TGFβ mRNA was expressed among low-grade and malignant gliomas, TGFβ was secreted in latent and/or active form into conditioned media and appeared to serve as an endogenous regulator of glioma proliferation in vitro. The mitogenic response, either positive or negative, correlated with the degree of anaplasia and karyotypic divergence.