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 Endproducts 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.

Retrospective Evaluation of Bone Turnover Markers in Serum for the Prediction of Metastases Development in Breast Cancer Patients: A Cohort Study

“…An interesting aspect, which is suggested by these findings, is the potential of BTMs to stratify patients at a high risk of (bone) metastatic disease and govern further treatments in the adjuvant setting to increase bone-metastasis-free survival; a comprehensive list of biomarkers is provided by Wang et al [ 28 ]. Interestingly, stronger evidence of this notion has arisen in the context of advanced disease [ 29 , 30 , 31 ]. D’Oronzo and colleagues recently studied 47 patients with bone metastatic BC who underwent BTM measurements and dual-energy X-ray absorptiometry (DXA) before bisphosphonate treatment.…”

Bone, a Secondary Growth Site of Breast and Prostate Carcinomas: Role of Osteocytes

“…Sclerostin, DKK-1, and FGF23 are osteocyte-specific markers; they were studied to evaluate their contribution to osteocyte/cancer cell crosstalk [ 24 , 33 , 60 ]. DKK-1 and sclerostin are negative regulators of the Wnt/β-catenin pathway; sclerostin is expressed almost exclusively in osteocytes at high levels, while DKK-1 is present throughout the body.…”

Osteomyelitis, Oxidative Stress and Related Biomarkers

“…The expression of RANKL in particular, among other genes, is a peculiar trait of the osteoblast lineage. Osteoblasts can also produce OPG, which acts as a decoy receptor, binding and blocking RANKL to inhibit osteoclasts activation and thus protect against bone loss [ 7 ]. Several studies have in fact proposed these new osteoimmunological biomarkers as useful tools in different conditions, for instance in assessing the progress of osteolytic bone metastases [ 7 ] or after total knee replacement surgery, to quantify the osteointegration of the prosthesis [ 8 ].…”