Schmid Michael C, Varner Judith A
Moores UCSD Cancer Center, University of California-San Diego, La Jolla, California, USA.
Methods Enzymol. 2008;445:343-71. doi: 10.1016/S0076-6879(08)03015-2.
Tumor growth and metastasis depend on neovascularization, the growth of new blood vessels. Recent studies have found that bone marrow derived cells contribute to angiogenesis during tumor growth and inflammation. Tumor neovascularization is regulated in part by monocytes, which are myeloid lineage cells from the bone marrow. Tumors exhibit significant monocyte infiltrates, and recent studies indicate that monocytes are actively recruited to the tumor microenvironment. Upon tumor infiltration, monocytes can participate in tumor neovascularization by differentiating into M2 macrophages, which express proangiogenic growth factors. By understanding how bone marrow-derived cells contribute to tumor growth, it may be possible to develop new approaches to cancer therapy. In this chapter, we discuss experimental methods to examine the roles of myeloid cells in tumor growth and angiogenesis, including methods to identify, isolate, purify, and characterize bone marrow-derived monocytes. We also outline methods to analyze the in vivo roles of myeloid cells in tumor growth and angiogenesis using adoptive transfer, bone marrow transplantation, tumor models and immunohistochemistry for markers of vessels and myeloid cells. Finally, we review methods to characterize myeloid cell trafficking in vitro and in vivo.
肿瘤的生长和转移依赖于新生血管形成，即新血管的生长。最近的研究发现，骨髓来源的细胞在肿瘤生长和炎症过程中有助于血管生成。肿瘤新生血管形成部分受单核细胞调节，单核细胞是来自骨髓的髓系细胞。肿瘤表现出显著的单核细胞浸润，最近的研究表明单核细胞被积极招募到肿瘤微环境中。肿瘤浸润后，单核细胞可通过分化为表达促血管生成生长因子的M2巨噬细胞参与肿瘤新生血管形成。通过了解骨髓来源的细胞如何促进肿瘤生长，有可能开发出新的癌症治疗方法。在本章中，我们讨论了检测髓系细胞在肿瘤生长和血管生成中作用的实验方法，包括鉴定、分离、纯化和表征骨髓来源单核细胞的方法。我们还概述了使用过继转移、骨髓移植、肿瘤模型以及针对血管和髓系细胞标志物的免疫组织化学来分析髓系细胞在肿瘤生长和血管生成中体内作用的方法。最后，我们综述了在体外和体内表征髓系细胞迁移的方法。
