The role of tumor microenvironment in prostate cancer bone metastasis
The role of tumor microenvironment in prostate cancer bone metastasis
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DOI：
10.1002/jcb.21214
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发表时间：
2007-07-01
影响因子：
4
通讯作者：
Vessella, Robert L.
中科院分区：
文献类型：
--
作者：
Morrissey, Colm;Vessella, Robert L.
前列腺癌（PCa）上皮细胞需要许多因子来促进其在远处转移部位的建立和生长。它们适应其微环境、增殖和募集下层基质的能力对于转移的存活和生长是不可或缺的。前列腺癌主要转移到骨，骨转移是发病的主要原因。骨髓为转移瘤的形成提供了一个允许的环境。在某些情况下，细胞可能会保持休眠一段时间，最终增殖，以响应一个未知的“触发”。“骨髓富含祖细胞，这些祖细胞分化成多种细胞类型，产生新的血管，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）。通过分泌大量细胞因子、生长因子和蛋白酶，它们募集产生功能性基质所需的辅助细胞。这些成分参与基质和PCa细胞之间的相互作用，允许肿瘤的生长和存活。如果不加以控制，一旦PCa肿瘤在骨髓中建立，它最终将取代骨髓，中断骨稳态，通常促进骨中的成骨细胞反应，包括骨坏死事件。新编织骨的大量沉积导致PCa骨转移患者的神经压迫、骨痛和骨折增加。本综述将探讨肿瘤微环境，其在促进肿瘤传播，生长和由此产生的病理与PCa骨转移的作用。
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 sometime, 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.