Longitudinal evaluation of Wnt inhibitors and comparison with others serum osteoimmunological biomarkers in osteolytic bone metastasis

Abstract

Bone and the immune system are closely linked: bone regulates the hematopoietic stem cells, which are precursors of immune cells, and several immunoregulatory cytokines influence the differentiation of bone cells, thus defining the osteoimmunological system. Cytokines and growth factors produced by immune and bone cells promote tumors in bone, supporting the vicious cycle of bone metastasis. Therefore osteoimmunological molecules linking the immune and bone systems could have diagnostic and prognostic potential for bone metastases. The osteoimmunologic Wnt pathway has been recently described as an important pathway with a vital role in bone carcinogenesis and metastatic progression. We examined the Wnt inhibitor DKK-1, sclerostin and several other osteoimmunological biomarkers involved in bone metastatic progression: RANKL, OPG, OPN, matrix metalloproteinase MMP-3 and the Receptor of Advanced Glycosylated End-products sRAGE. OPN and sclerostin proved good biomarkers of metastatic bone progression; the RANKL/OPG ratio was a good indicator of bone erosion in the metastatic process, while sRAGE had a protective role against metastatic progression in bone. These results serve to define a panel of new osteoimmunological biomarkers that could be useful in assessing the progress of osteolytic bone metastases.