LYMPHOKINE-ACTIVATED KILLER-CELLS INDUCE DIFFERENTIATION IN MCF-7 BREAST-CARCINOMA NODULES BUT NOT IN MASTOSIS NODULES MAINTAINED IN 3-DIMENSIONAL CULTURE

In order to better understand the interaction between activated lympho cytes and breast carcinoma cells, we studied the degree of infiltratio n, the membrane contacts established and their cytostatic and cytolyti c effects in MCF-7 nodules maintained in three-dimensional culture. A comparison was made with nodules of a nonmalignant, immortalized masto sis cell line. Histological, immunohistochemical and electron microsco pical observations were performed as well as DNA synthesis measurement s in the two components of the coculture. The lymphokine-activated kil ler (LAK) cells adhered more frequently to the carcinoma nodules than to the mastosis nodules. They actively penetrated into both of them. T he penetration remained peripheral, and only a few cells migrated more deeply. The LAK cells established close cell-to-cell contacts with th e two types of nodules, and intercellular gaps were formed: damaged ce lls could be seen near the activated killer cells. In MCF-7 nodules, a 5-fold inhibition of proliferation occurred, and extensive necrotic z ones developed; this was accompanied by a general tendency for glandul ar redifferentiation. In mastosis nodules, necrosis also developed but no cell differentiation occurred and proliferation was less inhibited (2 times). Interleukin-2 alone enhanced DNA synthesis in mastosis nod ules but had no effect on MCF-7 nodules, and no extending necrosis cou ld be seen in both types of nodules. The cytolytic effects of LAK cell s combined with their redifferentiating effect in MCF-7 breast carcino ma nodules may be a useful indication for further breast cancer therap y research.