The bone microenvironment in metastasis; what is special about bone?

Abstract

The skeleton is a common destination for many cancer metastases including breast and prostate cancer. There are many characteristics of bone that make it an ideal environment for cancer cell migration and colonization. Metaphyseal bone, found at the ends of long bone, in ribs, and in vertebrae, is comprised of trabecular bone interspersed with marrow and rich vasculature. The specialized microvasculature is adapted for the easy passage of cells in and out of the bone marrow. Moreover, the metasphyseal regions of bone are constantly undergoing remodeling, a process that releases growth factors from the matrix. Bone turnover also involves the production of numerous cytokines and chemokines that provide a means of communication between osteoblasts and osteoclasts, but co-incidentally can also attract and support metastatic cells. Once in the marrow, cancer cells can interact directly and indirectly with osteoblasts and osteclasts, as well as hematopoietic and stromal cells. Cancer cells secrete factors that affect the network of cells in the bone microenvironment as well as interact with other cytokines. Additionally, transient cells of the immune system may join the local mileau to ultimately support cancer cell growth. However, most metastasized cells that enter the bone marrow are transient; a few may remain in a dormant state for many years. Advances in understanding the bone cell-tumor cell interactions are key to controlling, if not preventing metastasis to bone.