Relationship between tumour cell morphology, gap junctions and susceptibility to cytolysis by tumour necrosis factor

Tumour necrosis factor (TNF) is directly cytolytic to certain tumour cell lines in vitro, although TNF-resistant variants can be selected from these susceptible lines by exposure to TNF. While studying TNF-susceptible L929 cells and their resistant variant, L929/R, we noted that within L929 colonies the cells were widely spaced whereas they were closely packed in L929/R colonies. L929/R cells also adhered more strongly to plastic and differed from L929 in cell shape. Similar observations were made with TNF susceptible and resistant variants of two other cell lines (RK13 and a plastic adherent U937 subline). The tendency of resistant cells to grow closely together suggests the possibility of inter-cell communication for the TNF resistant state. However, like L929 and U937, L929/R and U937/R did not communicate by gap junctions and we could find no evidence of extracellular mediators of TNF resistance. Rather the differences in colonial morphology, cell shape and plastic adherence may be secondary to an underlying mechanism which defines TNF susceptibility/resistance.