Osteomimicry: Old concepts and new findings

The colonization of a distant organ by tumor cells is paradoxically an inefficient process, since a very small percentage of circulating tumor cells (CTCs) will escape the different strategies put in place by the organism to neutralize them, eventually reaching a secondary site. Bone is the primary target tissue for metastases in patients affected by breast and prostate cancers, likely representing the best “soil” for these cancer cells to grow. To adapt to the bone microenvironment tumor cells are required to express bone-related genes. This phenomenon is known as osteomimicry, which allows osteotropic tumor cells to “hide” and grow undisturbed within the bone tissue and to dramatically disrupt its homeostasis. Acquisition of osteomimicry is a multistep process by which cancer cells acquire osteoblasts-like gene and protein profiles. Besides the classical expression of the bone matrix proteins, which are a clear hallmark of osteoblast mimicry, several other molecules related to osteoblast physiology have been identified over the years, acting as important mediators of this phenomenon. These include pro-osteomimetic transcription factors, osteoclast-regulating factors, and osteogenic pathways. In addition, novel osteomimetic modulators have been discovered in the recent years. In this chapter, we will give an overview of the osteoblast physiology and functions and we will illustrate the concept of osteomimicry in the context of the vicious cycle, highlighting new findings that are contributing to our understanding of this intricate puzzle.