Bussard Karen M, Gay Carol V, Mastro Andrea M
Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA.
Cancer Metastasis Rev. 2008 Mar;27(1):41-55. doi: 10.1007/s10555-007-9109-4.
The skeleton is a common destination for many cancer metastases including breast and prostate cancer. There are many characteristics of bone that make it an ideal environment for cancer cell migration and colonization. Metaphyseal bone, found at the ends of long bone, in ribs, and in vertebrae, is comprised of trabecular bone interspersed with marrow and rich vasculature. The specialized microvasculature is adapted for the easy passage of cells in and out of the bone marrow. Moreover, the metasphyseal regions of bone are constantly undergoing remodeling, a process that releases growth factors from the matrix. Bone turnover also involves the production of numerous cytokines and chemokines that provide a means of communication between osteoblasts and osteoclasts, but co-incidentally can also attract and support metastatic cells. Once in the marrow, cancer cells can interact directly and indirectly with osteoblasts and osteclasts, as well as hematopoietic and stromal cells. Cancer cells secrete factors that affect the network of cells in the bone microenvironment as well as interact with other cytokines. Additionally, transient cells of the immune system may join the local mileau to ultimately support cancer cell growth. However, most metastasized cells that enter the bone marrow are transient; a few may remain in a dormant state for many years. Advances in understanding the bone cell-tumor cell interactions are key to controlling, if not preventing metastasis to bone.
骨骼是包括乳腺癌和前列腺癌在内的许多癌症转移的常见靶点。骨骼具有许多特性，使其成为癌细胞迁移和定植的理想环境。干骺端骨位于长骨末端、肋骨和椎骨中，由散布着骨髓和丰富脉管系统的小梁骨组成。特殊的微血管系统便于细胞进出骨髓。此外，骨骼的干骺端区域不断进行重塑，这一过程会从基质中释放生长因子。骨转换还涉及多种细胞因子和趋化因子的产生，这些因子为成骨细胞和破骨细胞之间提供了一种通讯方式，但巧合的是，它们也能吸引并支持转移细胞。一旦进入骨髓，癌细胞可直接或间接与成骨细胞、破骨细胞以及造血细胞和基质细胞相互作用。癌细胞分泌影响骨微环境中细胞网络的因子，并与其他细胞因子相互作用。此外，免疫系统的短暂细胞可能会加入局部环境，最终支持癌细胞生长。然而，大多数进入骨髓的转移细胞都是短暂的；少数可能会处于休眠状态多年。了解骨细胞与肿瘤细胞之间的相互作用进展是控制（即便无法预防）骨转移的关键。
