Natural host resistance and in vivo selection of malignant tumour cells.

In cells transformed in vitro by different agents we have identified two discrete characteristics essential for in vivo selection by the effectors of host natural resistance. These two biochemically distinct characteristics, ie resistance to hydrogen peroxide and ability to secrete E type prostaglandin (PGE) in contact with NK cells, macrophages and neutrophils, may both be expressed either in about 100% of cells transformed by Rous sarcoma virus, or in less than 0.1% of cells transformed spontaneously. The expression of these characteristics provides the cells with selective advantages in vivo and determines the level of their tumorigenic activity and experimental metastasis-forming activity. These characteristics are apparently necessary, but insufficient, for spontaneous metastasizing activity. Demonstrated NK resistance of malignant cell variants is directly connected with their ability to produce PGE. The in vitro transformed cells which do not possess these qualities apparently have no ability for in vivo survival and growth. Though these two cellular properties are connected with biochemically different pathways (catabolism of H2O2 and metabolism of arachidonic acid) they are jointly expressed, or not expressed, in transformed cells. The possible mechanisms of in vivo selection of malignant cell variants, with one or a few cell properties united in clusters, and the dual role of natural resistance in this process are discussed.