Transforming growth factor-beta production and induction of cellular responses in 13762NF rat mammary adenocarcinoma cell clones.

We characterized three clones of different metastatic capacity (MTC, MTLn2 and MTLn3) derived from the 13762NF rat mammary adenocarcinoma for their production and response to TGF-beta. All three clones expressed comparable amounts of TGF-beta 1 mRNA and secreted 100-300 pg/10(6) cells/24 h in a soluble latent form. TGF-beta was found in extracellular matrices produced by all three tumor clones. Addition of exogenous TGF-beta induced different responses. While the low metastatic clone MTC was highly sensitive to the growth inhibitory effect of TGF-beta (ID50 approximately 50 pg/ml), a 6-fold higher dose was necessary for the high metastatic clone MTLn3 (ID50 approximately 300 pg/ml). The clone with intermediate metastatic potential MTLn2 was unresponsive to TGF-beta (1 pg/ml to 3 ng/ml). Our data suggest that tumor cells can modulate their biological properties in an autocrine and/or paracrine fashion by virtue of expression of TGF-beta.