**4.4 Osteomimicry**

Osteomimicry describes the phenomenon where osteotropic cancer cells express proteins and receptors found on bone cells and the bone matrix. It was speculated that such measures allow cancer cells to evade the immune system and/or establish in the bone microenvironment (122,123). These proteins include but are not limited to osteocalcin, osteopontin, alkaline phopsphatase and Runx2 (124). Osteoblast transcription factor Runx2 is ectopically expressed by breast cancer cells and stimulates their proliferation, motility, and invasion through increased MMP9 expression from both cancer cells and osteoblasts (125,126). Runx2 has also been shown to regulate TGF-influenced PTHrP levels, as well as upregulate Indian hedgehog (127). Breast cancer cells express Hedgehog ligands that activate osteopontin expression in osteoclasts, promoting osteoclast maturation and resorptive activity through upregulated Cathepsin K and MMP9 (128,129). Of interest, expression of anti-resorptive OPG has been demonstrated to correlate with increased bonespecific homing and colonization potential in breast cancer cells (122), and to promote cancer cell survival (130,131). Osteoclastic intergrin v3 (54), has been shown to be upregulated in metastatic versus primary tumour cells, and has been identified as a critical mediator of breast cancer metastasis to bone (107,132). It is unclear whether cells from the primary tumour display osteomimetic features that allow their metastasis to bone, or whether secondary tumour cells established in the bone marrow and matrix receive environmental factors that give them their osteomimetic features. Regardless, the ability of cancer cells to produce many of these factors has been beneficial to thrive in the bone microenvironment.
