Factors regulating the growth of metastatic cancer in bone

Metastatic tumor cells can interfere directly with the function of bone cel ls involved in normal bone remodeling or indirectly by influencing the beha vior of hematopoietic, stromal and other cells in bone marrow that interact with bone cells. Recent studies of metastatic cancer have revealed that tu mor cells interact closely with vascular endothelial cells, basement membra ne and bone marrow stromal cells through cell surface proteins or by releas ing factors which affect the function of these cells. Bidirectional interac tion between marrow cells and tumor cells can give the latter a selective a dvantage for growth in bone which can lead to the destruction of or to incr eased production of bone matrix. Understanding of the mechanisms involved i n tumor metastasis and growth in bone has increased in recent years, and in this review we shall describe current knowledge of these mechanisms and of the predilection of certain types of cancers to metastasize to bone, their growth in the bone microenvironment and interactions between them and bone cells. Because metastatic breast cancer has been studied more than any oth er, we shall focus on it as a representative example, although the general principles apply to other types of cancer and to myeloma.