Role of Macrophage Polarization in Tumor Angiogenesis and Vessel Normalization: Implications for New Anticancer Therapies - International Review of Cell and Molecular Biology - page 15

Figure 1.1 Schematic representation of signaling pathways in macrophage polariza-
tion. Macrophage polarization-related factors in the tumor microenvironment exert
their effects through macrophage surface receptors to trigger intracellular signaling
pathways, such as mTOR, NF- κ B, Notch, Stat6, PPAR γ and c-Myc, which in turn induce
gene transcription. By sensing the differently transcribed gene products, macrophages
are polarized to classically activated (M1) or alternatively activated (M2) phenotype,
which, respectively, inhibits and promotes tumor angiogenesis and progression. For
color version of this igure, the reader is referred to the online version of this topic.
5. ROLE OF TAM s AND THEIR POLARIZATION IN
TUMOR ANGIOGENESIS
5.1. Role and Mechanisms of TAMs
In most tumors, blood vessels are dramatically increased during the transition
from benign to malignant states, a process regarded as an angiogenic switch
and that is influenced by the tumor microenvironment ( Qian and Pollard,
2010 ). The potential role of macrophages in modulating tumor angiogenesis
was first proposed by Sunderkotter et al. in 1991 ( Sunderkotter et al., 1991 ).
After that, a variety of studies have shown that TAMs are often found in the
surrounding of blood vessels of solid tumors ( Leek et al., 1996 ; Negus et al.,
1997 ; Ohno et al., 2004 ). As shown in Table 1.2 , studies in human tumors
demonstrate a positive correlation between blood vessel density and the