The link between bone-derived factors osteocalcin, fibroblast growth factor 23, sclerostin, lipocalin 2 and tumor bone metastasis

Abstract

The skeleton is the third most common site of metastatic disease, which causes serious bone complications and short-term prognosis in cancer patients. Prostate and breast cancers are responsible for the majority of bone metastasis, resulting in osteolytic or osteoblastic lesions. The crosstalk between bone cells and their interactions with tumor cells are important in the development of lesions. Recently, both preclinical and clinical studies documented the clinical relevance of bone-derived factors, including osteocalcin (OC) and its undercarboxylated form (ucOC), fibroblast growth factor 23 (FGF23), sclerostin (SCL), and lipocalin 2 (LCN2) as prognostic tumor biomarkers and potential therapeutic targets in bone metastasis. Both OC and ucOC could be useful targets for the prevention of bone metastasis in breast cancer. Moreover, elevated OC level may be a metastatic marker of prostate cancer. FGF23 is particularly important for those forms of cancer that primarily affect bone and/or are characterized by bone metastasis. In other tumor entities, increased FGF23 level is enigmatic. SCL plays a significant role in the pathogenesis of both osteolytic and osteoblastic lesions, as its levels are high in metastatic breast and prostate cancers. Elevated expression levels of LCN2 have been found in aggressive subtypes of cancer. However, its role in anti-metastasis varies significantly between different cancer types. Anyway, all aforementioned bone-derived factors can be used as promising tumor biomarkers. As metastatic bone disease is generally not curable, targeting bone factors represents a new trend in the prevention of bone metastasis and patient care.

Expression of Immune-Related and Inflammatory Markers and Their Prognostic Impact in Colorectal Cancer Patients

“…Additionally, we did not observe significant expression of CHIT, pentraxin-3, sTNF-R1, sTNF-R2, and osteocalcin. However, some articles reported the expression of these immune and inflammatoryrelated markers in tumor cells and their implications in tumor biology, contrary to our findings [15,[41][42][43][44][45][46]. Lee et al [42] performed immunohistochemistry to measure the expression of immune markers in tumor cells in a cohort of 395 colorectal cancer patients.…”

“…Based on the information obtained from reference studies [15,18,32,34,[41][42][43][44][45][46]48,49], we screened several markers related to malignancy and performed preliminary tests at the RNA level through quantitative PCR (qPCR). After conducting the qPCR analysis, we selected the following 12 markers that exhibited high expression levels and decided to include them in our research: APRIL/TNFSF13, BAFF, LAG-3, PD-1, PD-L1, CTLA-4, CHIT, MMP-3, osteocalcin, pentraxin-3, sTNF-R1, and sTNF-R2.…”

Assessment of bone turnover markers and DXA parameters to predict bone metastasis progression during zoledronate treatment: a single-center experience

“…Nevertheless, both the decrease in OC and the increase in OPG are not surprising findings. OC is the most abundant non-collagenous protein in bone and is released into systemic circulation during bone resorption [ 36 ], a process known to be negatively modulated by zoledronate. On the other hand, OPG is a marker of osteoblast differentiation [ 37 ], which is fostered by bisphosphonates [ 38 , 39 ].…”

Role of Erk5 expressed in bone marrow mesenchymal stem cells on bone homeostasis and its potential applications in cancer treatment

“…Bone tissue not only plays a fundamental role in locomotion, protection of organ and storage for minerals (calcium and phosphate), but also has an endocrine function in secreting hormones, and osteocalcin (secreted by osteoblasts) serves a variety of roles, including regulation of energy metabolism [ 7 ]. In recent years, the association between osteocalcin and cancer has been studied, and it has been suggested that osteocalcin is relevant to bone metastasis of breast and prostate cancers [ 8 ]. Serum osteocalcin levels were significantly elevated in LepR-Cre ; Erk5 fl/fl mice, suggesting that Erk5 in BM-MSCs might be a new drug target to inhibit bone metastasis in these cancers [ 6 ].…”