Studies on cell transformation.

Seven different transformation stigmata of the transformed CHO cell line, including morphological characteristics, growth behavior, cell membrane biochemical properties, and failure of fibronectin deposition, are reversed by addition of cAMP derivatives to the medium. Simultaneously the microtubular pattern changes from a sparse, relatively random set to an orderly arrangement of tubules largely parallel to each other and to the long axis of the resulting fibroblastic cell. Agents like colcemid and cytochalasin B, respectively disorganizing microtubular and particular microfilamentous structures, prevent at least certain aspects of the reverse transformation reaction induced by cAMP in interphase cells. It is proposed that malignant transformation can be effected by damage to the microtubular and microfilamentous structures which changes cell constitution and behavior in two ways: (1) chromosomal instability is introduced which promotes continuous selection for variants better able to resist environmental signals to limit reproduction and (2) a variety of metabolic defects in biochemical processes such as specific membrane functions are introduced which may alter the growth responses of the cell. This picture offers a reasonable explanation for a number of aspects of normal and malignant cell behavior.