The Role of Tumor Microenvironment in Cancer Metastasis: Molecular Mechanisms and Therapeutic Opportunities
Abstract
Simple Summary
Abstract
1. Introduction
2. Roles of Cellular TME Components in Regulating the Metastatic Cascade
2.1. Role of Immune Cells in Modulating Cancer Metastasis
2.2. Role of Mesenchymal Stem Cells in Regulating Metastasis
2.3. Cancer-Associated Fibroblasts in Promoting Metastasis
2.4. Endothelial Cells Attract Cancer Cells to the Metastatic Site
2.5. Components in the Blood Microenvironment That Facilitate Metastasis
3. Role of Extracellular TME Components in Tumor Progression
3.1. Role of the ECM in Cancer Metastasis
3.2. Hypoxic Microenvironment as a Major Driver of Cancer Metastasis
4. Targeting Cellular Constituents of the TME to Block Metastasis
4.1. TAMs as a Promising Target against Cancer Metastasis
4.2. Exploiting Cancer-Associated Mesenchymal Stroma/Stem-Like Cells to Control Metastasis
4.3. Targeting the Blood Microenvironment
5. Strategies to Improve Tumor Oxygenation and Therapeutic Efficacy
5.1. Remodeling the Tumor Vasculature
5.2. Stroma Normalization Strategy to Target Hypoxia
6. Discussion—Future Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
5′-FU | 5′-fluorouracil |
APCs | antigen presenting cells |
ATX | autotaxin |
BM | basement membrane |
BM-MSCs | bone marrow-derived mesenchymal stem cells |
CAFs | cancer associated fibroblasts |
CA-MSC | cancer-associated MSC |
CB2 | cannabinoid receptor 2 |
CAIX | carbonic anhydrase |
CCL2 | chemokine (C-C motif) ligand 2 |
CTCs | circulating tumor cells |
CTMs | circulating tumor microemboli |
CSF-1 | colony-stimulating factor-1 |
CRC | colorectal cancer |
PDAC | pancreatic ductal adenocarcinoma |
endMT | endothelial-to-mesenchymal transition |
EMT | epithelial-to-mesenchymal transition |
ECM | extracellular matrix |
FAP | fibroblast activation protein |
GC-MSCs | gastric cancer tissue-related mesenchymal stem cells |
AuNPs | gold nanoparticles |
GPCRs | G-protein coupled receptors |
GM-CSF | granulocyte-macrophage colony-stimulating factor |
HNSCC | head and neck squamous cell carcinoma |
HSC | hematopoietic stem cells |
HCC | hepatocellular carcinoma |
IMs | inflammatory monocytes |
IFN-γ | interferon-γ |
KCNN4 | intermediate-conductance Ca2+-activated potassium channels |
LECs | lymphatic endothelial cells |
LPA | lysophosphatidic acid |
LOX | lysyl oxidase |
MMPs | matrix metalloproteinases |
MSCs | mesenchymal stem cells |
MMT | mesenchymal-mesenchymal transition |
MAMs | metastasis-associated macrophages |
NPs | nanoparticles |
NK | natural killer cells |
NSCLC | non-small cell lung cancer cells |
PDX | patient-derived xenograft mouse |
PD-L1 | programmed death-ligand 1 |
PRL-3 | phosphatase of regenerating liver |
S-TRAIL | secretable tumor necrosis factor apoptosis inducing ligand |
sECM | synthetic extracellular matrix |
TSP | thrombospondin |
TLRs | toll-like Receptors |
TME | tumor microenvironment |
TMEM | tumor microenvironment of metastasis |
TNF-α | tumor necrosis factor-α |
TAMs | tumor-associated macrophages |
VCAM-1 | vascular cell adhesion molecule-1 |
α-SMA | α-smooth muscle actin |
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Neophytou, C.M.; Panagi, M.; Stylianopoulos, T.; Papageorgis, P. The Role of Tumor Microenvironment in Cancer Metastasis: Molecular Mechanisms and Therapeutic Opportunities. Cancers 2021, 13, 2053. https://doi.org/10.3390/cancers13092053
Neophytou CM, Panagi M, Stylianopoulos T, Papageorgis P. The Role of Tumor Microenvironment in Cancer Metastasis: Molecular Mechanisms and Therapeutic Opportunities. Cancers. 2021; 13(9):2053. https://doi.org/10.3390/cancers13092053
Chicago/Turabian StyleNeophytou, Christiana M., Myrofora Panagi, Triantafyllos Stylianopoulos, and Panagiotis Papageorgis. 2021. "The Role of Tumor Microenvironment in Cancer Metastasis: Molecular Mechanisms and Therapeutic Opportunities" Cancers 13, no. 9: 2053. https://doi.org/10.3390/cancers13092053
APA StyleNeophytou, C. M., Panagi, M., Stylianopoulos, T., & Papageorgis, P. (2021). The Role of Tumor Microenvironment in Cancer Metastasis: Molecular Mechanisms and Therapeutic Opportunities. Cancers, 13(9), 2053. https://doi.org/10.3390/cancers13092053