Changes in response to, and production of, transforming growth factor type β during neoplastic progression in cultured rat tracheal epithelial cells

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Abstract
As rat tracheal epithelial cells progress from a normal to a neoplastic phenotype there are systematic changes in their ability to produce and activate latent transforming growth factor type β (TGF-β) as well as systematic changes in their response to this growth factor. Using a TGF-β radioreceptor binding competition assay it was found that normal proliferating rat tracheal cells in early primary culture produced latent TGF-β. With the emergence of terminally differentiated cell populations active TGF-β was also detected in the conditioned medium. When normal cells were cultured under conditions allowing for condinued proliferation, no active TGF-β was detected in the conditioned medium. Colonies of proliferating epithelial cells in 4–6 week primary cultures or subculturable trachelial cell lines did not produce detectable levels of active or latent growth factor. With neoplastic progression there was likewise a change in response to active TGF-β. Normal tracheal cells in primary culture were highly sensitive to growth-factor-induced decreases in thymidine uptake as well as to the induction of terminal differentiation. Proliferating epithelial cells in late (4–6 week) primary cultures and preneoplastic, subculturable cell lines were often as sensitive as normal cells to the growth factor-induced decline in thymidine uptake. None of these altered populations, however, was induced to differentiate (to form cornified, cross-linked envelopes) in the presence of TGF-β.