Growth suppression of transformed BALB/c 3T3 cells by transforming growth factor {beta}1 occurs only in the presence of their normal counterparts

Transforming growth factor ß1 (TGF-ß1) enhancesthe yield of transformed foci of BALB/c 3T3 cells, but the continuouspresence of TGF-ß1 after foci formation inhibits thegrowth of transformed foci. The focus-forming ability of Ha-ras-,v-src-and PyMT-transformed cells growing on a monolayer of non-transformedcells was completely suppressed by TGF ß1, whereasgrowth of the transformed cells was little inhibited by TGF-ß1in the absence of their normal counterparts. The inhibitionby TGF-ß1 of focus formation by transformed BALB/c3T3 cells on a normal cell monolayer remained when TGF-ß1was removed from the culture medium after 2 weeks. However,the transformed cells were not killed, since they grew in cultureconditions under which only transformed cells are able to grow(soft agar). These results suggest that TGF-ß1 suppressesgrowth of transformed cells in the presence of normal cells.Furthermore, when non-transformed cells were treated with TGF-ß1before co-culture with Ha-ras-transformed cells, formation oftransformed foci was inhibited. When normal and transformedcells were cultured in the same dish but separated physically,focus formation was still Inhibited. On the other hand, TGF-ß1enhanced the growth and changed the morphology of non-transformedcells only in the presence of transformed counterparts. Thegrowth inhibitory effect of TGF-ß1 on transformedcells and its growth stlmulatory effect on non-transformed cellsin co-culture conditions suggest the induction of reciprocalparacrine growth regulatory factors. As TGF-ß1 inhibitsthe growth of transformed BALB/c 3T3 cells only in the presenceof their normal counterparts, a paracrine negative growth controlmechanism appears to be operating.