Biology of Tumor Cells

Tumor biologists can mimic the progression process in vitro, but only to a very limited degree (8; Fig. 1). Normal cells can be explanted from an animal into culture, but they only have a limited life-span.

After a few rounds of cell division, the culture will undergo a "crisis" with most cells dying, but a few cells survive. These are cells that have undergone a genetic change and have become immortalized; that is, they can grow and divide indefinitely in culture. Such cells can then be further transformed by oncogenic agents. This term "transformation" can be defined as the acquisition of growth characterisics not exhibited by the parental cells.

Immortalization is itself a transformation step, and once a cell has been transformed once, it can be transformed again. There is therefore a hierarchy of transformed phenotypes (Fig. 1). The ability to grow in low serum (that is, the ability to grow in the absence of certain growth factors and nutrients) is a less stringent assay of transformation than growth to high saturation density (which is the ability to grow without growth being inhibited by neighboring cell; that is, the phenomenon of contact inhibition is lost). This is a less stringent assay than the ability to grow without a substratum (or anchorage-independent growth), which is a less stringent assay than tumor production in animals Thus progression to a pathologically more destructive phe-notype can be mimicked in vitro, and we can hypothesize that each step in ihe progression of a tumor is caused by a gene, and such a gene could be called an oncogene.

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