CD44 in Bone Metastasis Development: A Key Player in the Fate Decisions of the Invading Cells?

A participant in key developmental processes, the adhesion glycoprotein CD44 is also expressed in several types of malignancies and can promote metastasis. In addition, the expression of CD44 isoforms in different types of cancer such as prostate and breast cancers may facilitate bone metastases by enhancing tumorigenicity, osteomimicry, cell migration, homing to bone, and anchorage within the bone specialized domains. Moreover, there is evidence that the CD44-ICD fragments in breast cancer cells may promote the cells' osteolytic nature. Yet the mechanisms by which CD44 and its downstream effectors promote the establishment of these cells within the bone are not fully elucidated. In this review, we summarize the current data on the roles played by CD44 in cancer progression and bone metastasis and the possible effects of its interaction with the different components of the bone marrow milieu.