Progressive loss of shape-responsive metabolic controls in cells with increasingly transformed phenotype.

The modulation of cell metabolism by cell shape and external surface contact has been studied by suspension culture of anchorage-dependent fibroblasts. The suspended cells shut down protein synthesis and nuclear RNA metabolism and cease replicating DNA. However, these responses to suspension are lost or modified as cells become progressively transformed in behavior. We compare the metabolic consequences of suspension culture in five related types of fibroblasts: the well regulated mouse diploid fibroblast; the spontaneously immortalized and progressively less well regulated lines 3T3, 3T6 and HDP3T6; and the fully transformed anchorage-independent SVPy3T3. Protein synthesis is inhibited rapidly following suspension in diploid fibroblasts and more slowly in the less well regulated cells. In contrast, the response of hnRNA synthesis to suspension is lost completely when cells adopt the 3T6 phenotype, and message regulation is lost in HDP3T6. The prompt inhibition of ribosomal RNA precursor is modified to a slow decline in HDP3T6. The metabolism of fully transformed SVPy3T3 cells is indifferent to suspension. The progressive loss of shape-responsive controls may be related to tumor progression.