ANTITUMOR ACTIONS OF CYTOKINES ON NEW HUMAN PAPILLARY THYROID-CARCINOMA CELL-LINES

To investigate the in vitro effects of cytokines on the growth of huma n papillary thyroid carcinoma (PTC) cells, we established six new PTC cell lines, designated BHP 5, 14, 15, 17, 18, and 19, from different p atients. We studied the antiproliferative actions of cytokines by usin g BHP cells, NP cells (PTC cell. line), and ARO cells (anaplastic thyr oid carcinoma cell line). These cells were treated with various concen trations of tumor necrosis factor-alpha (TNF alpha), interferon-gamma (IFN gamma), interleukin-1 beta (IL-1 beta), and transforming growth f actor-beta 1 (TGF beta 1), alone and in combination. Cell proliferatio n was assessed by [H-3]thymidine incorporation and cell number measure ment. In BHP cell lines, IFN gamma, IL-1 beta, and TGF beta 1 inhibite d [H-3]thymidine incorporation and decreased cell number, but TNF alph a stimulated [H-3]thymidine incorporation. In NP cells, treatment with each cytokine decreased [H-3]thymidine incorporation and cell number. In contrast, the proliferation of ARO cells was either stimulated by or resistant to TNF alpha, IL-1 beta, and TGF beta 1. The effects of t hese cytokines on [H-3]thymidine incorporation were additive in these cell lines. The results suggest that IL-1 beta and TGF beta 1 play a p ivotal role in growth inhibition of PTC cells, and the escape from neg ative control of IL-1 beta and TGF beta 1 may be a step toward anaplas tic changes. The additive effects of these cytokines suggest that they act through different pathways.