Role of stromal‐derived cytokines and growth factors in bone metastasis

BACKGROUND Interactions between bone marrow‐derived cytokines, growth factors, and tumors play a critical role in both the homing of tumors to the bone and the development of bone metastasis. Bone is a storehouse of latent growth factors produced by stromal cells and osteoblasts that, when activated during osteoclastic bone resorption, can enhance the growth of tumor cells. METHODS This article reviews the role these factors may play in bone metastasis. RESULTS Several studies have shown that breast carcinoma cells, which induce osteoclastic bone resorption, release growth factors that enhance tumor growth. In addition, bone‐derived growth factors and chemokines, such as stromal cell‐derived factor 1 and monocyte chemoattractant protein 1, can act as chemoattractants to attract tumor cells to bone. Finally, the interaction between tumor cells and bone marrow stromal cells can result in increased production of cytokines and growth factors, such as interleukin 6 or the ligand for the receptor activator of nuclear factor κB, that can enhance bone destruction, tumor growth, and angiogenesis. CONCLUSIONS Stromal cell‐derived cytokines and growth factors as well as growth factors that are released during the bone resorption process play a critical role in the development of bone metastasis. Interruption of this symbiotic relation between tumors that induce bone destruction and release of bone‐derived growth factors can have beneficial effects on blocking both bone destruction and decreasing tumor burden within bone. Cancer 2003;97(3 Suppl):733–8. © 2003 American Cancer Society. DOI 10.1002/cncr.11148