Sottnik Joseph L, Zhang Jian, Macoska Jill A, Keller Evan T
Department of Urology, University of Michigan, RM 5308 CC, Ann Arbor, MI, 48109-8940, USA.
Cancer Microenviron. 2011 Dec;4(3):283-97. doi: 10.1007/s12307-011-0073-8. Epub 2011 Jul 5.
The tumor microenvironment (TME) is a very complex niche that consists of multiple cell types, supportive matrix and soluble factors. Cells in the TME consist of both host cells that are present at tumor site at the onset of tumor growth and cells that are recruited in either response to tumor- or host-derived factors. PCa (PCa) thrives on crosstalk between tumor cells and the TME. Crosstalk results in an orchestrated evolution of both the tumor and microenvironment as the tumor progresses. The TME reacts to PCa-produced soluble factors as well as direct interaction with PCa cells. In return, the TME produces soluble factors, structural support and direct contact interactions that influence the establishment and progression of PCa. In this review, we focus on the host side of the equation to provide a foundation for understanding how different aspects of the TME contribute to PCa progression. We discuss immune effector cells, specialized niches, such as the vascular and bone marrow, and several key protein factors that mediate host effects on PCa. This discussion highlights the concept that the TME offers a potentially very fertile target for PCa therapy.
肿瘤微环境(TME)是一个非常复杂的生态位,由多种细胞类型、支持性基质和可溶性因子组成。TME中的细胞既包括肿瘤生长开始时就存在于肿瘤部位的宿主细胞,也包括因肿瘤或宿主衍生因子而被招募的细胞。前列腺癌(PCa)在肿瘤细胞与TME之间的相互作用中蓬勃发展。随着肿瘤的进展,相互作用导致肿瘤和微环境的协同进化。TME对PCa产生的可溶性因子以及与PCa细胞的直接相互作用做出反应。作为回报,TME产生影响PCa的建立和进展的可溶性因子、结构支持和直接接触相互作用。在本综述中,我们关注等式中的宿主方面,为理解TME的不同方面如何促进PCa进展提供基础。我们讨论免疫效应细胞、特殊生态位,如血管和骨髓,以及几种介导宿主对PCa影响的关键蛋白质因子。这一讨论突出了TME为PCa治疗提供潜在非常丰富靶点的概念。