EXPRESSION OF TRANSCRIPTS OF INTERLEUKIN-6 AND RELATED CYTOKINES BY HUMAN BREAST-TUMORS, BREAST-CANCER CELLS, AND ADIPOSE STROMAL CELLS

The expression of transcripts of cytokines of the interleukin-6 (IL-6) family has been examined in human breast tumors, breast cancer cell l ines, and adipose stromal cells, by means of reverse transcription pol ymerase chain reaction amplification. Of the six breast tumor samples examined, all expressed transcripts encoding IL-6, and Leukemia Inhibi tory Factor (LIF). Four of the samples also expressed transcripts for oncostatin M(OSM) and IL-11, end three expressed the IL-6 receptor. Ad ipose stromal cells expressed IL-6, IL-11 and LIF, but not the IL-6 re ceptor. consistent with previous conclusions that IL-6 activity in the se cells required addition of IL-6 soluble receptor. In the case of T4 7D cells, expression of IL-11 protein was confirmed by immunotitration . Moreover, in these cells, expression of IL-11 transcripts was induce d 3-fold by addition of estradiol to the culture medium. These results add credence to our previous proposal that breast cancer development is regulated in part by local autocrine and paracrine mechanisms via e pithelial/mesenchymal interactions, in which estrogen produced by stro mal cells surrounding the tumor acts to stimulate the production of gr owth factors and cytokines by the tumor cells. Some of these may act t o stimulate further the growth and development of the tumor, while the se or other factors may act on the surrounding mesenchymal cells in a paracrine fashion to stimulate aromatase expression in the presence of glucocorticoids. Thus, a positive feedback loop is established which leads to the development and growth of the tumor.