The role of bone microenvironment, vitamin D and calcium.
Starting  first from Paget's "seed and soil" to the latest hypothesis about metastatic process involving the concept of a premetastatic niche, a large amount of data suggested the idea that metastatization is a multistep coordinated process with a high degree of efficiency. A specific subpopulation of cells with tumor-initiating and migratory capacity can selectively migrate toward sites that are able to promote survival, and/or proliferation of metastatic tumor cells through a microenvironment modification. Bone plays a pivotal role in this process, acting not only as a preferential site for cancer cells' homing and proliferation, due to a complex interplay between different cellular phenotypes such as osteoblasts and osteoclasts, but also as a source of bone marrow precursors that are able to facilitate the metastatic process in extra-skeletal disease. Moreover, bone microenvironment has the unique capacity to retain cancer stem cells in a quiescent status, acting as a reservoir that is able to cause a metastatic spread also many years after the resection of the primary tumor. To add a further level of complexity, these mechanisms are strictly regulated through the signalling through several soluble factors including PTH, vitamin D or calcium concentration. Understanding this complexity represents a major challenge in anti-cancer research and a mandatory step towards the development of new drugs potentially able not only to reduce the consequences of bone lesions but also to target the metastatization process from the "bone pre-neoplastic niche" to "visceral pre-neoplastic niches".
University Campus Bio-Medico, Via Alvaro del Portillo, Rome, Italy. d.santini@unicampus.it
Daniele
D
Santini
Francesco
F
Pantano
Bruno
B
Vincenzi
Giuseppe
G
Tonini
Francesco
F
Bertoldo
D000818:Animals; D001859:Bone Neoplasms / Q000378:metabolism* / Q000473:pathology*; D002118:Calcium / Q000378:metabolism*; D060833:Cellular Microenvironment; D006801:Humans; D014807:Vitamin D / Q000378:metabolism*
D014807:Vitamin D; D002118:Calcium