University of Athens School of Medicine, Alexandra General Hospital, Department of Clinical Therapeutics, 80 Vas. Sofias Avenue, 11528, Athens, Greece.
Expert Opin Ther Targets. 2012 Aug;16(8):761-9. doi: 10.1517/14728222.2012.697154. Epub 2012 Jul 5.
Sclerostin is a cysteine-knot-containing protein, which is produced by osteocytes and inhibits osteoblast function. The aim of this review is to summarize the data about the role of sclerostin in cancer-induced bone disease.
We performed a thorough search for articles in the PubMed using the words "sclerostin, cancer, multiple myeloma", and for similar abstracts that were presented in the ASH and ASCO annual meetings (2005 - 2011). In multiple myeloma, sclerostin is produced by myeloma cells and elevated in the serum or the plasma of the patients, and correlates with extensive bone disease and adverse myeloma features. In prostate cancer, sclerostin expression is reduced and in combination with bone morhogenetic protein-6 and noggin expression may serve as prognostic predictor for metastatic progression. In breast cancer, in vitro data suggest that the malignant cell induces the expression of sclerostin to inhibit osteoblasts in the metastatic bone area.
Sclerostin may play a role in inhibiting bone formation in the biology of bone metastases in breast cancer and of myeloma-related bone disease. The results of phase I/II studies with anti-sclerostin drugs in subjects with low bone mass may lead to the potential clinical investigation of these agents in cancer-induced bone disease.
骨硬化蛋白是一种含半胱氨酸的蛋白,由骨细胞产生,可抑制成骨细胞的功能。本文旨在总结骨硬化蛋白在癌症相关性骨病中的作用数据。
我们在 PubMed 上使用“骨硬化蛋白、癌症、多发性骨髓瘤”等关键词进行了全面检索,并对 2005-2011 年 ASH 和 ASCO 年会上的类似摘要进行了检索。在多发性骨髓瘤中,骨硬化蛋白由骨髓瘤细胞产生,在患者的血清或血浆中升高,并与广泛的骨病和不良的骨髓瘤特征相关。在前列腺癌中,骨硬化蛋白的表达减少,与骨形态发生蛋白-6 和 noggin 的表达相结合可能作为转移性进展的预后预测因子。在乳腺癌中,体外数据表明,恶性细胞诱导骨硬化蛋白的表达,以抑制转移骨区的成骨细胞。
骨硬化蛋白可能在乳腺癌骨转移和骨髓瘤相关骨病的骨形成抑制生物学中发挥作用。在低骨量患者中进行抗骨硬化蛋白药物的 I/II 期研究的结果可能会促使这些药物在癌症相关性骨病中的潜在临床研究。