Mukaida Naofumi, Zhang Di, Sasaki So-Ichiro
Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan.
Cancers (Basel). 2020 Oct 9;12(10):2896. doi: 10.3390/cancers12102896.
Bone metastasis is frequently complicated in patients with advanced solid cancers such as breast, prostate and lung cancers, and impairs patients' quality of life and prognosis. At the first step of bone metastasis, cancer cells adhere to the endothelium in bone marrow and survive in a dormant state by utilizing hematopoietic niches present therein. Once a dormant stage is disturbed, cancer cells grow through the interaction with various bone marrow resident cells, particularly osteoclasts and osteoblasts. Consequently, osteoclast activation is a hallmark of bone metastasis. As a consequence, the drugs targeting osteoclast activation are frequently used to treat bone metastasis but are not effective to inhibit cancer cell growth in bone marrow. Thus, additional types of resident cells are presumed to contribute to cancer cell growth in bone metastasis sites. Cancer-associated fibroblasts (CAFs) are fibroblasts that accumulate in cancer tissues and can have diverse roles in cancer progression and metastasis. Given the presence of CAFs in bone metastasis sites, CAFs are emerging as an important cellular player in bone metastasis. Hence, in this review, we will discuss the potential roles of CAFs in tumor progression, particularly bone metastasis.
骨转移在乳腺癌、前列腺癌和肺癌等晚期实体癌患者中经常出现，会损害患者的生活质量和预后。在骨转移的第一步，癌细胞黏附于骨髓内皮，并通过利用其中存在的造血微环境以休眠状态存活。一旦休眠阶段被打破，癌细胞就会通过与各种骨髓驻留细胞，特别是破骨细胞和成骨细胞相互作用而生长。因此，破骨细胞活化是骨转移的一个标志。结果，靶向破骨细胞活化的药物经常被用于治疗骨转移，但对抑制骨髓中的癌细胞生长无效。因此，推测还有其他类型的驻留细胞在骨转移部位促进癌细胞生长。癌症相关成纤维细胞（CAFs）是积聚在癌症组织中的成纤维细胞，在癌症进展和转移中可能发挥多种作用。鉴于骨转移部位存在CAFs，CAFs正在成为骨转移中一个重要的细胞参与者。因此，在本综述中，我们将讨论CAFs在肿瘤进展，特别是骨转移中的潜在作用。
