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Research Article

The Tumor Microenvironment: Key to Early Detection

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Pages 393-425 | Published online: 10 Oct 2008
 

Abstract

The tumor microenvironment plays an important role equal to the tumor cell population in the progression of cancer. Consisting of stromal fibroblasts, inflammatory cells, components of the vasculature, normal epithelia, and extracellular matrix, the surrounding environment interacts or “cross-talks” with tumor cells through the release of growth factors, cytokines, proteases, and other bioactive molecules. Tumor growth, formation of new vascular networks, evasion of the host immune system, and invasion and metastasis are processes that co-evolve and become finely optimized and regulated within the tumor microenvironment. However, relatively recent reports on three areas of study have come together to add new levels of complexity to the tumor microenvironment. These include ectodomain shedding of proteins, shedding of membrane-derived vesicles, and novel roles for phospholipids. These dynamic changes that take place in the tumor microenvironment provide new avenues for study and for the early detection of cancer, whereas proteomic technologies provide the means to detect these unique proteins and lipids. Here we review the evolving concepts of the tumor microenvironment that, together with advances in proteomic technologies, hold the promise to facilitate the detection of early-stage cancer.

Abbreviations and Glossary
ATX=

autotaxin, identical to the LPA-producing enzyme lysophospholipase D (lysoPLD)

CAF=

carcinogenic-associated fibroblast

c-Met=

product of the proto-oncogene c-met, also known as the hepatocyte growth factor receptor

E-Cadherin=

epithelial cadherin

EC=

endothelial cell

ECM=

extracellular matrix

EGF=

epidermal growth factor

EMMPRIN=

extracellular matrix metalloproteinase inducer

EMT=

epithelial-to-mesenchymal transition

EOC=

epithelial ovarian carcinoma

FasL=

Fas ligand

FGF=

fibroblast growth factor

FGFR=

fibroblast growth factor receptor

FSP=

fibroblast-secreted protein

GPCR=

G-Protein coupled receptor

HB-HGF=

heparin-binding epidermal growth factor-like growth factor

HGF=

hepatocyte growth factor

HGF/SF=

hepatocyte growth factor/scatter factor

HRCC=

human renal carcinoma cells

HSPG=

heparan-sulfate proteoglycan

IGF=

insulin-like growth factor

IL=

interleukin

IOSE-29=

immortalized ovarian surface epithelial cell line 29

LPA=

lysophosphatidic acid

LPC=

lysophosphatidylcholine

LPS=

lipopolysaccharide

lysoPLD=

lysophospholipase D

MAP=

mitogen-activated protein

MCP=

monocyte chemoattractant protein

MF=

membrane fragments

MMP=

matrix metalloproteinase

MT1-MMP=

membrane-type 1-matrix metalloproteinase, also known as MMP-14

N-Cadherin=

neuronal cadherin

NK=

natural killer

NO=

nitric oxide

PAF=

platelet-activating factor

PDGF=

platelet-derived growth factor

PKC=

protein kinase C

SPC=

sphingosylphosphorylcholine

S1P=

sphingosine-1-phosphate

Tie-1=

and Tie-2 are endothelial-specific receptor tyrosine kinases. Ligands for Tie-1 are not known; however, ligands for Tie-2 include the angiopoietins Ang-1 and Ang-2

TGF=

transforming growth factor

TNF=

tumor necrosis factor

uPA=

urinary-type plasminogen activator

uPAR=

urinary-type plasminogen activator receptor

VEGF=

vascular endothelial growth factor

VEGFR=

vascular endothelial growth factor receptor

Abbreviations and Glossary
ATX=

autotaxin, identical to the LPA-producing enzyme lysophospholipase D (lysoPLD)

CAF=

carcinogenic-associated fibroblast

c-Met=

product of the proto-oncogene c-met, also known as the hepatocyte growth factor receptor

E-Cadherin=

epithelial cadherin

EC=

endothelial cell

ECM=

extracellular matrix

EGF=

epidermal growth factor

EMMPRIN=

extracellular matrix metalloproteinase inducer

EMT=

epithelial-to-mesenchymal transition

EOC=

epithelial ovarian carcinoma

FasL=

Fas ligand

FGF=

fibroblast growth factor

FGFR=

fibroblast growth factor receptor

FSP=

fibroblast-secreted protein

GPCR=

G-Protein coupled receptor

HB-HGF=

heparin-binding epidermal growth factor-like growth factor

HGF=

hepatocyte growth factor

HGF/SF=

hepatocyte growth factor/scatter factor

HRCC=

human renal carcinoma cells

HSPG=

heparan-sulfate proteoglycan

IGF=

insulin-like growth factor

IL=

interleukin

IOSE-29=

immortalized ovarian surface epithelial cell line 29

LPA=

lysophosphatidic acid

LPC=

lysophosphatidylcholine

LPS=

lipopolysaccharide

lysoPLD=

lysophospholipase D

MAP=

mitogen-activated protein

MCP=

monocyte chemoattractant protein

MF=

membrane fragments

MMP=

matrix metalloproteinase

MT1-MMP=

membrane-type 1-matrix metalloproteinase, also known as MMP-14

N-Cadherin=

neuronal cadherin

NK=

natural killer

NO=

nitric oxide

PAF=

platelet-activating factor

PDGF=

platelet-derived growth factor

PKC=

protein kinase C

SPC=

sphingosylphosphorylcholine

S1P=

sphingosine-1-phosphate

Tie-1=

and Tie-2 are endothelial-specific receptor tyrosine kinases. Ligands for Tie-1 are not known; however, ligands for Tie-2 include the angiopoietins Ang-1 and Ang-2

TGF=

transforming growth factor

TNF=

tumor necrosis factor

uPA=

urinary-type plasminogen activator

uPAR=

urinary-type plasminogen activator receptor

VEGF=

vascular endothelial growth factor

VEGFR=

vascular endothelial growth factor receptor

Notes

*Editor's note: See Glossary.

*Editor's note: Refers to migration over a substrate-bound gradient, as opposed to “chemotactic” (where the gradient is soluble).

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