The comparative effects of tumor necrosis factor on tumor cells growing anchorage dependently and independently

Tumor necrosis factor (TNF) is a macrophage-derived cytokine that has been shown to exert differential cytotoxic and/or cytostatic effects on many human and animal tumor cells. In vitro assays of TNF effects have been performed mainly on cultured tumor cells growing as a monolayer. However, tumor cells may respond differently to the effects of growth factors depending on whether they grow in two-dimensional monolayer cultures or in three-dimensional colonies in soft agar. We have tested the effect of TNF on the anchorage-dependent (monolayer) and anchorage-independent (soft agar) growth of five rat, two mouse, and one human tumor cell lines. The results indicate that tumor cells may demonstrate different growth responses in these two culture conditions, and that some tumor cells that are resistant to the cytostatic effect of TNF in monolayer cultures may demonstrate significant sensitivity when growing in soft agar medium. One of the rat tumor cell lines unaffected by TNF in monolayer culture was actually stimulated in their colony growth in soft agar medium. The clonogenic techniques of cultivating human tumor cells in soft agar may be suitable for the screening of TNF-sensitive tumors for therapeutic consideration with this substance.