Biology Reference
In-Depth Information
The current review will summarize a comprehensive overview about the
basic biology of macrophages, monocytes recruitment and the polarization
of macrophages in the tumor microenvironment, as well as the function and
underlying mechanisms of TAM polarization in the regulation of tumor
angiogenesis and vessel normalization. Furthermore, the potential of target-
ing TAMs in the tumor microenvironment for anticancer therapy by tumor
angiogenesis inhibition and vessel normalization will also be discussed.
2. MACROPHAGES AND THEIR PHENOTYPES
Macrophages are a major population in the mononuclear phagocytic
lineage deriving from bone marrow progenitor cells (
Doulatov et al., 2010
).
In contrast to the other mononuclear phagocytic lineages, such as dendritic
cells (DCs), macrophages have a longer lifespan (from hours to possibly
years) and display proteolytic and catabolic activities, such as phagocytosis,
which allow them to be highly effective in the ingestion of pathogens,
in the clearance of dead cells and debris, and in the remodeling of tis-
sues (
Galli et al., 2011
). Macrophages can be subcategorized according to
their anatomical locations, and tissue-specific resident macrophages include
osteoclasts in bone, alveolar macrophages in lung, histiocytes in intersti-
tial connective tissues, microglia in brain, Kupffer cells in liver and splenic
macrophages in spleen. However, they may have similar functional abilities
following the appropriate stimuli (
Galli et al., 2011
). To distinguish them
from other cell types, macrophages can be characterized by their specific
markers. In mice, macrophages express CD11b, F4/80, and CSF-1R, but not
Gr1. In human, they display specific expression of CD68, CD163, CD312,
CD115 and CD16 (
Qian and Pollard, 2010
). On the other hand, macro-
phages themselves are also heterogeneous, and they can be divided into
M1 and M2 phenotypes according to the Th1/Th2 dichotomy (
Gordon
and Taylor, 2005
). M1 phenotype macrophages induce type I helper T cell
(Th1) response. This population of macrophages is activated by bacterial
moieties, such as lipopolysaccharide (LPS), and Th1 cytokine interferon-
gamma (IFN-γ). In contrast, M2 phenotype macrophages are involved in
type II helper T cell (Th2) response, and are activated by cytokines secreted
from Th2 cell, such as interleukin 4 (IL-4) and IL-13. These two pheno-
types of macrophages can be characterized by their different patterns of
gene and protein expression (
Table 1.1
). For example, M1 macrophages dis-
play a high expression of major histocompatibility complex (MHC) class II,
IL-12 and tumor necrosis factor-alpha (TNF-α), and also generate reactive
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