Department of Biomedical Sciences, University of Padova, Padova, Italy.
Int Rev Cell Mol Biol. 2013;301:1-35. doi: 10.1016/B978-0-12-407704-1.00001-4.
Angiogenesis, the formation of new capillary blood vessels from preexisting vasculature, is one of the hallmarks of cancer that is pivotal for tumor growth and metastasis. Tumor vessels are known to be abnormal, with typically aberrant, leaky and disordered vessels. Thus, the combination of angiogenesis inhibition and vessel normalization is a potential strategy for anticancer therapy. The solid tumor is composed of not only cancer cells, but also the nonmalignant resident stromal cells, such as bone-marrow-derived cells (BMDCs) and cancer-associated fibroblasts (CAFs). Tumor-associated macrophages (TAMs) are the most abundant cell components of BMDCs, which play a significant role in promoting tumor progression. Accumulating evidences from both patient biopsies and experimental animal models have shown that TAMs function in tumor angiogenesis and vessel abnormalization in a density- and phenotype-dependent manner. This chapter will discuss the evidence for the factors and signaling pathways that are involved in macrophage recruitment and polarization in the tumor microenvironment, and it summarizes the role and underlying molecular mechanisms of macrophage polarization in tumor angiogenesis and vessel normalization. In addition, an overview of the potential of targeting TAM polarization for anticancer therapy will be provided.
血管生成，即从预先存在的脉管系统中形成新的毛细血管，是癌症的标志之一，对肿瘤的生长和转移至关重要。众所周知，肿瘤血管是异常的，通常具有异常、渗漏和紊乱的血管。因此，抑制血管生成和血管正常化的联合是一种潜在的抗癌治疗策略。实体瘤不仅由癌细胞组成，还包括非恶性常驻基质细胞，如骨髓源性细胞（BMDCs）和癌相关成纤维细胞（CAFs）。肿瘤相关巨噬细胞（TAMs）是 BMDCs 中最丰富的细胞成分，在促进肿瘤进展方面发挥着重要作用。来自患者活检和实验动物模型的大量证据表明，TAMs 以密度和表型依赖的方式在肿瘤血管生成和血管异常化中发挥作用。本章将讨论参与肿瘤微环境中巨噬细胞募集和极化的因素和信号通路的证据，并总结巨噬细胞极化在肿瘤血管生成和血管正常化中的作用及其潜在的分子机制。此外，还将概述针对 TAM 极化的抗癌治疗的潜力。
