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Matrix Metalloproteinases’ Role in Tumor Microenvironment

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Tumor Microenvironment

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1245))

Abstract

Cancer cells evolve in the tumor microenvironment (TME) by the acquisition of characteristics that allow them to initiate their passage through a series of events that constitute the metastatic cascade. For this purpose, tumor cells maintain a crosstalk with TME non-neoplastic cells transforming them into their allies. “Corrupted” cells such as cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), and tumor-associated neutrophils (TANs) as well as neoplastic cells express and secrete matrix metalloproteinases (MMPs). Moreover, TME metabolic conditions such as hypoxia and acidification induce MMPs’ synthesis in both cancer and stromal cells. MMPs’ participation in TME consists in promoting events, for example, epithelial-mesenchymal transition (EMT), apoptosis resistance, angiogenesis, and lymphangiogenesis. MMPs also facilitate tumor cell migration through the basement membrane (BM) and extracellular matrix (ECM). The aim of the present chapter is to discuss MMPs’ contribution to the evolution of cancer cells, their cellular origin, and their influence in the main processes that take place in the TME.

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Abbreviations

5-FU:

5-Fluorouracil

ADAMS:

A disintegrin and metalloproteinases

ADAMTSs:

ADAMs with thrombospondin motifs

ADFs:

Adipocyte-derived fibroblasts

AM:

Adrenomedullin

AP-1:

Activator protein-1

AR:

Androgen receptor

ASCs:

Adipocyte/stromal stem cells

BASCs:

Bronchio-alveolar stem cells

bFGF2:

Basic fibroblast growth factor-2

BM:

Basement membrane

BMDMCs:

Bone marrow-derived mesenchymal stem cells

bmMSCs:

Bone marrow mesenchymal stem cells

CAAs:

Cancer-associated adipocytes

CAFs:

Cancer-associated fibroblasts

CCL2:

Chemokine C-C motif ligand 2

CM:

Conditioned medium

COX2:

Cyclooxygenase 2

CSCs:

Cancer stem cells

CXCL12:

C-X-C motif chemokine 12

CXCR4:

Chemokine receptor-4

DFSP:

Dermatofibrosarcoma protuberans

ECM:

Extracellular matrix

ECs:

Endothelial cells

EGFR:

Epidermal growth factor receptor

EMT:

Epithelial-mesenchymal transition

endMT:

Endothelial-mesenchymal transition

ENO-1:

Enolase-1

Epo:

Erythropoietin

ER:

Estrogen receptor

EREG:

Pan-HER ligand epiregulin

ERK:

Extracellular signal-regulated kinase

Et-1:

Endothelin-1

ETP:

Endotrophin

ETS:

E-twenty-six-1

EVs:

Extracellular vesicles

FASLG:

FAS ligand

FIH-1:

Factor-inhibiting HIF-1

FOXC2:

Forkhead box protein C2

FoxP3+:

Recruit forkhead box P3

Fru-2,6-P2:

Fructose 2-6 biphosphate

FSP-1:

Fibroblast-secreted protein-1

FZD:

Frizzled

GPI:

Glycosylphosphatidylinositol

GSCs:

Glioma stem cells

HA:

Hyaluronic acid

HGF:

Hepatic growth factor

HIFs:

Hypoxia-inducible factors

HSCs:

Hematopoietic stem cells

Hsp-90:

Heat shock protein-90

HuVECs:

Human umbilical vein endothelial cells

IFN-γ:

Interferon-γ

IGF-1:

Insulin-like growth factor-1

IL:

Interleukin

IL-2Rα:

Interleukin-2 receptor α

JNK:

c-Jun N-terminal kinase

KDR:

Kinase insert domain receptor

KIF1B:

Kinesin-like protein 1B

KitL:

Kit ligand

KLF8:

Kruppel-like factor 8

LECs:

Lymphatic endothelial cells

LLC:

Lewis lung carcinoma

LN:

Lymph node

LOX1:

Lectin-type oxidase LDL receptor 1

LPS:

Lipopolysaccharide

LRP1:

Low-density lipoprotein (LDL) receptor-related protein 1

LVs:

Lymph vessels

LYVE-1:

Lymphatic vessel endothelial hyaluronan receptor-1

MAPK:

Mitogen-activating protein kinase

MaSCs:

Mammary stem cells

MCP-1:

Monocyte chemotactic protein-1

MCs:

Mast cells

M-CSF:

Monocyte colony-stimulating factor

MDSCs:

Myeloid-derived suppressor cells

MHC:

Major histocompatibility complex

MICA:

MHC class I-related chain molecules A

MM:

Multiple melanoma

MMPs:

Matrix metalloproteinases

MMRN2:

Multimerin-2

MMT:

Mesenchymal-mesenchymal transition

MSLN F:

Mesothelin

MT-MMPs:

Membrane-type MMPs

NE:

Neutrophil elastase

NF-κB:

Nuclear factor κB

NGAL:

Neutrophil gelatinase-associated lipocalin

NGF:

Nerve growth factor

NHE1:

Na+/H+ exchanger 1

NK:

Natural killer

NKG2D:

Natural killer group 2D

NRP-2:

Neuropilin-2

NSCLC:

Non-small cell lung cancer

OPN-MZF1:

Osteospondin-myeloid zinc finger 1

PAI:

Plasminogen activator inhibitor

PAR-1:

Protease-activated receptor-1

PDA:

Pancreatic ductal adenocarcinoma

PDGF-BB:

Platelet-derived growth factor-BB

PDGFRβ:

Platelet-derived growth factor receptor β

PEA-3:

Polyoma enhancer activator protein-3

PECAM-1:

Platelet endothelial cell adhesion molecule-1

PF4:

Platelet factor-4

PFK-1:

Phosphofructokinase-1

PFK-2/FBPase-2:

6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase

PGK1:

Phosphoglycerate kinase-1

PI3K:

Phosphoinositide 3-kinase

PPARγ:

Peroxisome proliferator-activated receptor-γ

Rac:

Rho-related C3 botulinum toxin substrate

RANTES:

Regulated on activation, normal T cell expressed and secreted (CCL5)

ROCK:

rhoA-dependent kinase

ROS:

Reactive oxygen species

SCCs:

Squamous carcinoma cells

SCF:

Stem cell factor

SCs:

Stem cells

SDF-1:

Stromal cell-derived factor 1

sE-Cad:

Soluble E-cadherin

SERPINE1:

Serine protease inhibitor E1

sKitL:

Soluble kit ligand

Sp-1:

Specific protein-1

TAMs:

Tumor-associated macrophages

TANs:

Tumor-associated neutrophils

TCF:

T-cell factor

TECs:

Tumor endothelial cells

TFPI-2:

Tissue factor pathway inhibitor-2

TGFβ:

Transforming growth factor-β

TIGAR:

TP53-induced glycolysis and apoptosis regulator

TIMPs:

Tissue inhibitors of metalloproteinases

TME:

Tumor microenvironment

TNFRSF11B:

Tumor necrosis factor receptor superfamily member 11 b

TNFα:

Tumor necrosis factor-α

TXF/LEF1:

T-cell factor/lymphoid enhancer factor 1

uPAR:

Urokinase plasminogen activator receptor

VEGF:

Vascular endothelial growth factor

VHL:

Von Hippel-Lindau

VSMCs:

Vascular smooth muscle cells

ZEB1:

Zinc finger E-box-binding homeobox 1

α-SMA:

α-Smooth muscle actin

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Authors and Affiliations

  1. Laboratorio de Oncología Biomédica, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City, Mexico

    Georgina Gonzalez-Avila & A. Armando García-Hernández

  2. Departamento de Investigación en Hiperreactividad Bronquial, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City, Mexico

    Bettina Sommer

  3. Laboratorio de Biología Celular, Departamento de Fibrosis Pulmonar, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City, Mexico

    Carlos Ramos

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  1. Georgina Gonzalez-Avila
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  2. Bettina Sommer
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  3. A. Armando García-Hernández
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  4. Carlos Ramos
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  1. Department of Radiology, Columbia University Medical Center, New York, NY, USA

    Alexander Birbrair

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Gonzalez-Avila, G., Sommer, B., García-Hernández, A.A., Ramos, C. (2020). Matrix Metalloproteinases’ Role in Tumor Microenvironment. In: Birbrair, A. (eds) Tumor Microenvironment. Advances in Experimental Medicine and Biology, vol 1245. Springer, Cham. https://doi.org/10.1007/978-3-030-40146-7_5

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