Osteotropic Cancers: From Primary Tumor to Bone

Tumour-induced bone disease is a common clinical feature of hematological and metastatic solid cancer. Thus, numerous scientists have gained a better understanding of the mechanisms by which certain tumor types tend to invade specifically the bone. Firstly, Stephen Paget recognized the ‘seed and soil’ hypothesis, stating that cancer cells (the ‘seeds’) can only develop in secondary organs where the microenvironment (the ‘soil’- the bone) is permissive for their growth. Today, this theory has been enlarged to the metastatic process in general, because in order to grow in distant organs, tumor cells need special properties that suit them to those organs. Specifically, in order to metastasize to bone, cancer cells firstly detach from their tissue of origin, subsequently transit through circulation, reside in the bone marrow and acquire a bone cell-like phenotype responsible for bone establishment and invasion. Each step in the metastatic cascade is rich in biological targets and mechanistic pathways, which are summarized in this review.