Biology Reference
In-Depth Information
CHAPTER ONE
Role of Macrophage Polarization
in Tumor Angiogenesis and Vessel
Normalization: Implications for
New Anticancer Therapies
Peiwen Chen
1
, Paolo Bonaldo
1
Department of Biomedical Sciences, University of Padova, Padova, Italy
1
Corresponding authors: E-mail: peiwenchen08@gmail.com or bonaldo@bio.unipd.it
Contents
1. Introduction
2
2. Macrophages and Their Phenotypes
4
3. Recruitment of Monocytes into Tumors
6
4. Macrophages and Macrophage Polarization in the Tumorigenesis
8
4.1. Macrophages and Cancer
8
4.2. Macrophage Polarization in the Tumor Microenvironment
10
4.2.1. Macrophage Polarization-Related Factors in the Tumor Microenvironment
11
4.2.2. Molecular Mechanisms of Macrophage Polarization in the
Tumor Microenvironment
13
5. Role of TAM
s
and Their Polarization in Tumor Angiogenesis
15
5.1. Role and Mechanisms of TAMs
15
5.2. Role of Macrophage Polarization
18
6. Role of TAM
s
and Their Polarization in Vessel Normalization
19
7. Concluding Remarks
22
Abstract
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 angio-
genesis and vessel abnormalization in a density- and phenotype-dependent manner.
