Maroni Paola, Bendinelli Paola
IRCCS Istituto Ortopedico Galeazzi, Laboratory of Experimental Biochemistry & Molecular Biology, Via R. Galeazzi 4, 20161 Milano, Italy.
Dipartimento di Scienze Biomediche per la Salute; Università degli Studi di Milano, Via L. Mangiagalli 31, 20133 Milano, Italy.
Cancers (Basel). 2020 Jul 6;12(7):1812. doi: 10.3390/cancers12071812.
Bone is the primarily preferred site for breast and prostate cancer to metastasize. Bone metastases are responsible for most deaths related to breast and prostate cancer. The bone's particular microenvironment makes it conducive for the growth of cancer cells. Studies on bone metastasis have focused on the interaction between cancer cells and the bone microenvironment. Osteocytes, the most common cell type of bone tissue, have received little attention in bone metastasis, although they are master signal sensors, integrators, and skeleton transducers. They play an important role in regulating bone mass by acting on both osteoblasts and osteoclasts, through the release of proteins such as sclerostin, Dickkopf-1 (DKK-1), and fibroblast growth factor 23 (FGF23). Osteocytes have been extensively re-evaluated, in light of their multiple functions: with different experimental approaches, it has been shown that, indeed, osteocytes are actively involved in the colonization of bone tissue by cancer cells. The present review focuses on recent research on the role that osteocytes play in bone metastasis of breast and prostate cancers. Moreover, the studies here summarized open up perspectives for new therapeutic approaches focused on modulating the activity of osteocytes to improve the condition of the bone metastatic patients. A better understanding of the complex interactions between cancer cells and bone-resident cells is indispensable for identifying potential therapeutic targets to stop tumor progression and prevent bone metastases.
骨骼是乳腺癌和前列腺癌转移的主要首选部位。骨转移是导致大多数与乳腺癌和前列腺癌相关死亡的原因。骨骼独特的微环境有利于癌细胞生长。关于骨转移的研究主要集中在癌细胞与骨微环境之间的相互作用。骨细胞是骨组织中最常见的细胞类型,尽管它们是主要的信号传感器、整合器和骨骼转换器,但在骨转移中却很少受到关注。它们通过释放如硬化蛋白、Dickkopf-1(DKK-1)和成纤维细胞生长因子23(FGF23)等蛋白质,对成骨细胞和破骨细胞发挥作用,从而在调节骨量方面发挥重要作用。鉴于骨细胞的多种功能,人们对其进行了广泛的重新评估:通过不同的实验方法表明,骨细胞确实积极参与癌细胞对骨组织的定植。本综述重点关注骨细胞在乳腺癌和前列腺癌骨转移中作用的最新研究。此外,这里总结的研究为专注于调节骨细胞活性以改善骨转移患者病情的新治疗方法开辟了前景。更好地理解癌细胞与骨驻留细胞之间的复杂相互作用对于确定阻止肿瘤进展和预防骨转移的潜在治疗靶点是必不可少的。