Molecular Skeletal Biology Laboratory, Department of Trauma, Hand and Reconstructive Surgery, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
Institute of Biochemistry and Signal Transduction, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
Biomolecules. 2020 Feb 19;10(2):337. doi: 10.3390/biom10020337.
Bone is the most common metastatic site in breast cancer. Upon arrival to the bone, disseminated tumor cells can undergo a period of dormancy but often eventually grow and hijack the bone microenvironment. The bone marrow microenvironment consists of multiple cell types including the bone cells, adipocytes, endothelial cells, and nerve cells that all have crucial functions in the maintenance of bone homeostasis. Tumor cells severely disturb the tightly controlled cellular and molecular interactions in the bone marrow fueling their own survival and growth. While the role of bone resorbing osteoclasts in breast cancer bone metastases is well established, the function of other bone cells, as well as adipocytes, endothelial cells, and nerve cells is less understood. In this review, we discuss the composition of the physiological bone microenvironment and how the presence of tumor cells influences the microenvironment, creating a pathological crosstalk between the cells. A better understanding of the cellular and molecular events that occur in the metastatic bone microenvironment could facilitate the identification of novel cellular targets to treat this devastating disease.
骨骼是乳腺癌最常见的转移部位。到达骨骼后，播散的肿瘤细胞可能会经历一段休眠期，但最终往往会生长并劫持骨骼微环境。骨髓微环境由多种细胞类型组成，包括骨细胞、脂肪细胞、内皮细胞和神经细胞，它们在维持骨骼稳态方面都具有至关重要的功能。肿瘤细胞严重扰乱了骨髓中细胞和分子相互作用的紧密控制，为其自身的存活和生长提供了动力。虽然破骨细胞在乳腺癌骨转移中的作用已得到充分证实，但其他骨细胞、脂肪细胞、内皮细胞和神经细胞的功能则了解较少。在这篇综述中，我们讨论了生理骨骼微环境的组成以及肿瘤细胞如何影响微环境，从而在细胞之间产生病理性串扰。更好地了解转移性骨骼微环境中发生的细胞和分子事件，可能有助于确定治疗这种毁灭性疾病的新的细胞靶标。
