Stromal cells and myeloid leukemic cells: Are they friends? Or foes?

Abstract

An important question when designing targeted therapy by modulation of stromal cells in the leukemic microenvironment is whether the stromal-derived support of tumor cell growth can be halted by drugs including originally tumor supportive agents. We recently used an in vitro system to show that either bone marrow stromal cells as a feeder layer or lipopolysaccharides (LPS) in culture medium is required for the proliferation of murine myeloid tumor cells. However, the stromal-derived support of leukemic growth is strongly suppressed when LPS is coupled in the same culture. This opposing effect of stromal cells or LPS on the myeloid leukemic growth is due, at least in part, to the rapid secretion of interleukin 12, Fas ligand and tissue inhibitor of metalloproteinases-2 from stromal cells upon LPS stimulation. These results provide a proof of principle that stromal cells can be “re-educated” by therapeutic drugs to attenuate tumor cell proliferation through re-wiring the cytokine network in the tumor microenvironment, thus diverting the disease course of myeloid leukemia in the opposite direction.