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TGFβ 1 and TGFβ 2 are potential growth regulators for low‐grade and malignant gliomas in vitro : Evidence in support of an autocrine hypothesis
Author(s) -
Jennings Mark T.,
Maciunas Robert J.,
Carver Robert,
Bascom Charles C.,
Juneau Patrick,
Misulis Karl,
Moses Harold L.
Publication year - 1991
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910490124
Subject(s) - autocrine signalling , glioma , transforming growth factor beta , biology , transforming growth factor , cancer research , tgf beta signaling pathway , medicine , endocrinology , anaplastic astrocytoma , in vitro , tgf beta 1 , epidermal growth factor , cell culture , astrocytoma , genetics
Low‐grade astrocytomas, anaplastic astrocytomas and glio‐blastomas in vitro were found to ubiquitously produce the mRNA of transforming growth factor‐β (TGFβ). TGFβ 1 and TGFβ 2 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 TGFβ 1 and TGFβ 2 . in vitro . Most hyperdiploid glioblastomas showed a positive mitogenic response to exogenous TGFβ 1 and TGFβ 2 . 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 TGFβ 1 thus establishing the specificity of the response in vitro . TGFβ 1 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.