Transferrin receptor and 4F2 expression by NK-sensitive and NK-resistant tumour cell lines

Upon stimulation with a phorbol ester and known tumour promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), the human erythroleukemia K562 cell line, a standard target for human natural killer (NK) cells, shows a significant reduction in expression of transferrin receptors (TfR) and becomes resistant to NK-mediated cytolysis. Prompted by the initial finding that expression of TfRs by K562 cells correlates with target sensitivity to NK cytotoxicity, we have investigated the role of two proposed NK-target structures, the TfR and 4F2 molecule in three other tumour cell lines which vary in their susceptibility to NK activity. We report that similar to K562 cells, MOLT 4, Raji and HL60 cells demonstrate phorbol-ester-induced down-regulation of TfR expression. The expression of TfRs alone does not determine target sensitivity. However, TfRs are probably located close to the NK-target structure in NK-sensitive cell lines. Based on the properties of phorbol ester induction, it is possible that the NK-target molecule is down-regulated in response to phorbol ester induction in a similar, if not identical manner to that of the TfR; thus, rendering NK-sensitive cells resistant to NK killing, after TPA exposure. Conversely, the target molecule is probably upregulated in MOLT 4 cells after TPA treatment as indicated by the acquired sensitivity of these cells to NK-mediated cytolysis. The expression of 4F2 molecules was not influenced by TPA treatment and does not correlate with NK sensitivity.