Chantrain Christophe F, Feron Olivier, Marbaix Etienne, DeClerck Yves A
Division of Hematology-Oncology, Department of Pediatrics, Universite Catholique de Louvain, Brussels, Belgium.
Cancer Microenviron. 2008 Dec;1(1):23-35. doi: 10.1007/s12307-008-0010-7. Epub 2008 May 7.
The bone marrow constitutes an unique microenvironment for cancer cells in three specific aspects. First, the bone marrow actively recruits circulating tumor cells where they find a sanctuary rich in growth factors and cytokines that promote their proliferation and survival. When in the bone marrow, tumor cells profoundly affect the homeostasis of the bone and the balance between osteogenesis and osteolysis. As a consequence, growth and survival factors normally sequestered into the bone matrix are released, further fueling cancer progression. Second, tumor cells actively recruit bone marrow-derived precursor cells into their own microenvironment. When in the tumors, these bone marrow-derived cells contribute to an inflammatory reaction and to the formation of the tumor vasculature. Third, bone marrow-derived cells can home in distant organs, where they form niches that attract circulating tumor cells. Our understanding of the contribution of the bone marrow microenvironment to cancer progression has therefore dramatically improved over the last few years. The importance of this new knowledge cannot be underestimated considering that the vast majority of cancer treatments such as cytotoxic and myeloablative chemotherapy, bone marrow transplantation and radiation therapy inflict a trauma to the bone marrow microenvironment. How such trauma affects the influence that the bone marrow microenvironment exerts on cancer is still poorly understood. In this article, the reciprocal relationship between the bone marrow microenvironment and tumor cells is reviewed, and its potential impact on cancer therapy is discussed.
骨髓在三个特定方面构成了癌细胞独特的微环境。首先，骨髓积极招募循环肿瘤细胞，在那里它们会发现一个富含促进其增殖和存活的生长因子和细胞因子的庇护所。当肿瘤细胞进入骨髓后，会深刻影响骨骼的内环境稳定以及成骨与溶骨之间的平衡。结果，通常被隔离在骨基质中的生长和存活因子被释放出来，进一步推动癌症进展。其次，肿瘤细胞积极将骨髓来源的前体细胞招募到其自身的微环境中。当这些细胞进入肿瘤后，会引发炎症反应并促进肿瘤血管生成。第三，骨髓来源的细胞可以归巢到远处器官，在那里它们形成吸引循环肿瘤细胞的微环境。因此，在过去几年中，我们对骨髓微环境在癌症进展中的作用的理解有了显著提高。考虑到绝大多数癌症治疗方法，如细胞毒性和清髓性化疗、骨髓移植和放射治疗都会对骨髓微环境造成创伤，这种新知识的重要性不可低估。目前对于这种创伤如何影响骨髓微环境对癌症的作用仍知之甚少。在本文中，我们综述了骨髓微环境与肿瘤细胞之间的相互关系，并讨论了其对癌症治疗的潜在影响。
