Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0153690 (bone metastases)
 6,382 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The transcription factor runt-related transcription factor 2 (Runx2) is a master gene implicated in the osteogenic differentiation of mesenchymal stem cells, and thus serves a determinant function in bone remodelling and skeletal integrity. Various signalling pathways regulate Runx2 abundance, which requires a number of molecules to finely modulate its expression. Furthermore, this gene may be ectopically-expressed in cancer cells. Recent studies have reported the involvement of Runx2 in cell proliferation, epithelial-mesenchymal transition, apoptosis and metastatic processes, suggesting it may represent a useful therapeutic target in cancer treatment. However, studies evaluating this gene as a cancer marker are lacking. In the present study, Runx2 expression was analysed in 11 different cancer cell lines not derived from bone tumour. In addition, the presence of Runx2-related cell-free RNA was examined in the peripheral blood of 41 patients affected by different forms of tumours. The results demonstrated high expression levels of Runx2 in the cancer cell lines and identified the presence of Runx2-related cell-free RNA in the peripheral blood of patients with cancer. As compared with normal individuals, the expression level was increased by 14.2-fold in patients with bone metastases and by 4.01-fold in patients without metastases. The results of the present study therefore opens up the possibility to exploit Runx2 expression as a cancer biomarker allowing the use of minimally invasive approaches for diagnosis and follow-up.
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PMID:Runx2 expression: A mesenchymal stem marker for cancer. 2789 87

Advanced prostate cancer frequently metastasizes to bone and induces a mixed osteoblastic/osteolytic bone response. Standard treatment for metastatic prostate cancer is androgen-deprivation therapy (ADT) that also affects bone biology. Treatment options for patients relapsing after ADT are limited, particularly in cases where castration-resistance does not depend on androgen receptor (AR) activity. Patients with non-AR driven metastases may, however, benefit from therapies targeting the tumor microenvironment. Therefore, the current study specifically investigated bone cell activity in clinical bone metastases in relation to tumor cell AR activity, in order to gain novel insight into biological heterogeneities of possible importance for patient stratification into bone-targeting therapies. Metastasis tissue obtained from treatment-naïve (n = 11) and castration-resistant (n = 28) patients was characterized using whole-genome expression analysis followed by multivariate modeling, functional enrichment analysis, and histological evaluation. Bone cell activity was analyzed by measuring expression levels of predefined marker genes representing osteoclasts (ACP5, CTSK, MMP9), osteoblasts (ALPL, BGLAP, RUNX2) and osteocytes (SOST). Principal component analysis indicated a positive correlation between osteoblast and osteoclast activity and a high variability in bone cell activity between different metastases. Immunohistochemistry verified a positive correlation between runt-related transcription factor 2 (RUNX2) positive osteoblasts and tartrate-resistant acid phosphatase (TRAP, encoded by ACP5) positive osteoclasts lining the metastatic bone surface. No difference in bone cell activity was seen between treatment-naïve and castration-resistant patients. Importantly, bone cell activity was inversely correlated to tumor cell AR activity (measured as AR, FOXA1, HOXB13, KLK2, KLK3, NKX3-1, STEAP2, and TMPRSS2 expression) and to patient serum prostate-specific antigen (PSA) levels. Functional enrichment analysis indicated high bone morphogenetic protein (BMP) signaling in metastases with high bone cell activity and low tumor cell AR activity. This was confirmed by BMP4 immunoreactivity in tumor cells of metastases with ongoing bone formation, as determined by histological evaluation of van Gieson-stained sections. In conclusion, the inverse relation observed between bone cell activity and tumor cell AR activity in prostate cancer bone metastasis may be of importance for patient response to AR and/or bone targeting therapies, but needs to be evaluated in clinical settings in relation to serum markers for bone remodeling, radiography and patient response to therapy. The importance of BMP signaling in the development of sclerotic metastasis lesions deserves further exploration.
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PMID:Bone Cell Activity in Clinical Prostate Cancer Bone Metastasis and Its Inverse Relation to Tumor Cell Androgen Receptor Activity. 2967