Stimulation of human prostatic carcinoma cell growth by factors present in human bone marrow

Malignant prostatic carcinoma, a major cause of cancer mortality in males, most often metastasizes to secondary sites in bone. Frequently, the growth rate of the secondary tumor in bone marrow is considerably greater than that of the slowly growing primary prostatic tumor. We now report that two lines of human prostatic carcinoma cells proliferate in response to conditioned media from unstimulated human, rat, or bovine bone marrow. Nonprostatic tumor cell lines showed little or no growth response to the same medium. The proliferative activity found in bone marrow was not duplicated by any of a variety of purified growth factors including epidermal growth factor (EGF), acidic or basic fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), transforming growth factor (TGF) alpha or beta, interleukins 1, 2, 3, 4 or 6, granulocyte (G), macrophage (M) or granulocyte-macrophage (GM) colony stimulating factor (CSF). Whereas a mixture of G-CSF, M-CSF, and IL 3 produced a mitogenic response in the prostatic carcinoma cells, these three factors were not present in our bone marrow samples in sufficient quantities to promote the observed proliferative response. To further identify the cellular source of the proliferative activity present in bone marrow-conditioned medium, we tested conditioned media made from human bone marrow stromal cells. The stromal cell conditioned medium stimulated increased growth of the prostatic carcinoma cells to levels equivalent to those observed with the bone marrow conditioned medium. These results suggest that novel mitogenic factors that are produced by bone marrow stromal cells and remain in the bone marrow cavity may account, in part, for the preferential growth of prostatic metastases in bone.