LYMPHOCYTE AND MONOCYTE-INDUCED MOTILITY OF MCF-7 CELLS BY TUMOR-NECROSIS-FACTOR-ALPHA

A potentially important tumor-host interaction is increased tumor-cell invasiveness in response to motility factors derived from stromal and lymphoid cells. Conditioned medium of IL-2-stimulated lymphocytes and fractions enriched in either T cells, natural killer (NK) cells, or m onocytes induced motility in MCF-7 breast carcinoma cells. ELISA and a ntibody neutralization studies demonstrated that this effect was due t o tumor necrosis factor-alpha (TNF-alpha) secretion by the lymphoid ce lls or the enriched fractions. Unstimulated leukocytes in direct conta ct with MCF-7 cells also induced motility that was inhibited by anti-T NF-alpha antiserum. Time-lapse video microscopy of cells exposed to 10 ng/ml TNF-alpha showed that motility was independent of its toxic eff ects. Immunoperoxidase showed that MCF-7 cells expressed both the 55-k Da and the 75-kDa TNF-alpha receptors (TNFR). Antiserum against the 55 -kDa TNFR like TNF-alpha, induced motility in MCF-7 cells. This was mo st likely due to cross-linking of the 55-kDa TNFR monomers, since the monomeric F(ab) did not produce this effect. Our results raise the pos sibility that TNF-alpha-induced motility is one mechanism by which tum or cells overcome the potential anti-tumor immune function of lymphocy tes and macrophages in peri-tumoral infiltrates. (C) 1997 Wiley-Liss, Inc.