Leukemic cells modulate induction of COX-2 in human stromal fibroblasts

The interaction of cancer cells with surrounding normal tissue cells is of utmost importance for their survival and tumor progression. For these purposes the cancer cells exploit normal tissue responses associated with inflammation and tissue repair. In the immediate tumor microenvironment one of the early stromal markers is cyclooxygenase-2 (COX-2). In this study we evaluated the effect of leukemia cell lines on nemosis-induced COX-2 expression in stromal fibroblasts. We found that THP-1 cells were the most potent leukemic cells (IC50=746) to suppress COX-2 expression. The U-937 cell line exhibited similar suppressive potency (IC50=921), whereas the KG-1 cell line (IC50=3519) was the least potent to affect COX-2 expression in the stromal cells. Our study shows that human leukemic cells can actively participate in modulation of stromal inflammation via inhibition of COX-2 expression. In a co-culture model of leukemia cell lines and stromal fibroblasts, our data suggest that the tumor-stromal interactions are complexly regulated, and the straightforward association of COX-2 expression with tumor progression may require re-evaluation since some tumor cells, e.g. from hematologic malignancies, may differentially modulate inflammation and COX-2 expression.