Cell-adhesion-disrupting action of interleukin 6 in human ductal breast carcinoma cells.

Abstract

Recombinant baculovirus-derived interleukin 6 (IL-6) disrupts the attachment of human ductal breast carcinoma subline ZR-75-1-Tx cells to neighbors and the substratum in culture without inhibiting the proliferation ofthe cells. The nonadherent cells lack pseudopodia and do not translocate directionally. These findings stand in contrast to the earlier observations in the Ro subline of ZR-75-1 cells in which 11-6 induces cell-cell separation without detachment of the cells from the substratum, with the cells displaying pseudopodia, increased motility, and decreased proliferation. The IL-6-induced ZR-75-1-Tx cell detachment and rounding are reversible by incubation of the treated cells in IL-6-free medium for several days. The distinctive changes induced by 11-6 in ZR-75-1-Ro cells are similarly reversible. Either acidic fibroblast growth factor or phorbol 12-myrisate 13-acetate can replace serum as a cofactor in IL-6-induced ZR-75-1-Tx cell detachment. Our findings indicate that genetic changes can occur in breast carcinoma cells that through cytokine action markedly affect cell structure, adhesiveness, and motility.Infiltrating ductal breast carcinoma is characterized by disordered cell adherence (1). Cell distribution in cytological preparations varies from minimally dyshesive multilayered sheets to small piled groups and isolated cells. Both the degree of dyshesion and extent of nuclear alteration depend on the differentiation of the carcinoma (1). Poorly differentiated tumors are characterized by the presence of many dyshesive groups and isolated cells. The other cardinal feature of ductal breast carcinoma is that once obvious neoplasia develops genetic defects multiply and accumulate (2).Earlier studies identified interleukin 6 (IL-6) as a cytokine that can act on epithelioid breast carcinoma cells in culture to induce conversion to a fibroblastoid phenotype accompanied by cell-cell separation and increased cell motility with cells in preformed colonies moving apart (3-5). These studies were carried out with T-47D (6) and ZR-75-1 (7) (henceforth called ZR-75-1-Ro subline) cells, in which IL-6 suppressed cell proliferation. An examination of IL-6 action on the clone B subline of ZR-75-1 cells (8, 9) revealed a modified response: IL-6 did not cause cell-cell separation in preformed colonies or inhibit the proliferation of clone B cells, but it did prolong the interval between mitosis and readherence of daughter cells, presumably because of somewhat decreased adhesivity of the IL-6-treated cells (10).These findings led to the investigation of a third subline of ZR-75-1 cells (11, 12), henceforth called ZR-75-1-Tx cells. We now report that in these cells IL-6 disrupts both cell-cell and cell-substratum adhesion: cells round up and are unable to translocate directionally; however, they continue to proliferate at an undiminished rate. MATERIALS AND METHODSCells. The ZR-75-1 cell line was obtained from C. Kent Osborne (The University of Texas Health Science Center at San Antonio) (11,12) in January 1992 and ...

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