肿瘤微环境在前列腺癌骨转移中的作用。
The role of tumor microenvironment in prostate cancer bone metastasis.
作者信息
Morrissey Colm, Vessella Robert L
机构信息
Department of Urology, University of Washington, Seattle, WA 98195, USA.
出版信息
J Cell Biochem. 2007 Jul 1;101(4):873-86. doi: 10.1002/jcb.21214.
Prostate cancer (PCa) epithelial cells require a number of factors to facilitate their establishment and growth at a distant site of metastasis. Their ability to adapt to their microenvironment, proliferate and recruit an underlying stroma is integral to the survival and growth of the metastasis. PCa predominantly metastasizes to the bone, and bone metastases are the main cause of morbidity. The bone marrow provides a permissive environment for the formation of a metastasis. In some cases, the cells may remain dormant for some time, eventually proliferating in response to an unknown "trigger." The marrow is rich in progenitor cells that differentiate into numerous cell types, producing new blood vessels, supporting fibroblasts, and an underlying extracellular matrix (ECM) that form the reactive stroma. By secreting a number of cytokines, growth factors and proteases they recruit auxiliary cells required to produce a functional stroma. These components are involved in a reciprocal interaction between the stroma and the PCa cells, allowing for the growth and survival of the tumor. Left unchecked, once a PCa tumor has established itself in the bone marrow it will eventually replace the marrow, interrupting bone homeostasis and typically promoting an osteoblastic response in the bone including osteoclastic events. The abundant deposition of new woven bone results in nerve compression, bone pain and an increase in fractures in patients with PCa bone metastases. This review will examine the tumor microenvironment, its role in facilitating tumor dissemination, growth and the resultant pathologies associated with PCa bone metastasis.
前列腺癌(PCa)上皮细胞需要多种因子来促进其在远处转移部位的定植和生长。它们适应微环境、增殖并募集潜在基质的能力对于转移灶的存活和生长至关重要。PCa主要转移至骨骼,骨转移是发病的主要原因。骨髓为转移灶的形成提供了适宜的环境。在某些情况下,细胞可能会休眠一段时间,最终在未知“触发因素”的作用下增殖。骨髓富含祖细胞,这些祖细胞可分化为多种细胞类型,产生新血管、支持成纤维细胞以及形成反应性基质的潜在细胞外基质(ECM)。它们通过分泌多种细胞因子、生长因子和蛋白酶来募集产生功能性基质所需的辅助细胞。这些成分参与了基质与PCa细胞之间的相互作用,从而使肿瘤得以生长和存活。如果不加以控制,一旦PCa肿瘤在骨髓中定植,它最终将取代骨髓,破坏骨稳态,并通常会促进骨中的成骨反应,包括破骨细胞事件。新编织骨的大量沉积会导致神经受压、骨痛以及PCa骨转移患者骨折增加。本综述将探讨肿瘤微环境,其在促进肿瘤播散、生长以及与PCa骨转移相关的病理结果方面的作用。