In Vitro Assays for Tumors Grown In Vivo: A Review of Kinetic Techniques

This review of in vitro kinetic techniques for experimental tumors concentrates on methods developed in tumor systems that grow in both the animal and in tissue cultures, and for which cells can be cloned from either growth mode. The ability of cells isolated from these solid tumors to form colonies when plated at low density in tissue culture is widely accepted as a test of their clonogenicity in radiobiology and experimental chemotherapy. It is assumed, but not proven, that a single cell that is capable of proliferating into a large colony in tissue culture would be capable of dividing and repopulating a tumor if left in situ in the experimental animal. “Clonogen” is thus defined operationally. This assumption, if valid, allows for the study of the kinetics of the clonogenic tumor cells, rather than the total tumor parenchymal cell population. The clonogenic potential of subpopulations of tumor cells, separated or identified in various ways, and changes in growth kinetics of stem cells during and after a course of antitumor therapy have been major areas of investigation. Techniques have been developed that allow one to infer the cytokinetics of tumor cells in situ by directly examining the growth and cloning efficiency of the isolated tumor cells when placed in culture. Several questions may be asked.