Biologic Manifestations of Oncogenesis In Vitro: A Critique1

Abstract
We distinguished between oncogenesis in vitro and cell transformation and suggestedthatthe term “transformed” be restricted to those cells demonstrated to grow as malignant neoplasms in vivo or be qualified to indicate the type of change observed. We have selected, from the many responses of cells to oncogenic viruses and carcinogens, those that appear to be associated with acquisition of neoplastic potential. These include alterations in cell and colony morphology and changes in growth properties. The changes in growth pmperties include the capacity for growth in fluid or agar suspension, loss of densitydependent inhibition of growth, and enhanced growth under conditions of reduced serum concentration. These criteria of neoplastic transtormatlen must be used cautiously and cannot completely replace the in vivo assay for tumor production. We interpreted certain of the morphologic changes and the reduced sensitivity of neoplastic cells to inhibition of growth at high cell density as resulting from reduced cytoplasmic spreading associated with diminished adhesiveness to substrate and to adjacent cells. Loss of surface substrate dependence and changes in dynamic morphology, rather than loss of contact inhibition of locomotion or mitosis, seem to characterize the neoplastic transformation of cells in vitro.