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Tumor microenvironment: a main actor in the metastasis process

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Abstract

Over recent decades, various studies have argued that the metastatic tissue microenvironment is fully controlled by the intrinsic properties of the cancer cells (growth, motility and invasion, angiogenesis, extracellular matrix remodeling, immune escape) and additional cells types. Overall, the extrinsic factors and determinants mediate the contribution of the host microenvironment to metastasis formation. The tumor microenvironment carries out these functions by secretion of molecules that can influence and modulate its phenotype, making these complex interactions the basis for support for the progression of a cancer. Here, we undertake a summary of the “state of the art” of the functions and actions of these cells, as the main actors in the promotion of the formation of the microenvironment of the metastatic niche, and the associated network of interactions. The unraveling of the relationships between tumorigenic cells and their microenvironment represents an important issue for the development of new therapeutic agents that can fight both initiation and recurrence of cancer.

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Abbreviations

ECM:

Extracellular matrix

CAFs:

Cancer-associated fibroblasts

MHC:

Major histocompatibility complex

TAMs:

Tumor-associated macrophages

MDSCs:

Myeloid-derived suppressor cells

TNC:

Tenascin C

MCP1:

Monocyte chemotactic protein 1

IL:

Interleukin

MMP:

Matrix metalloproteinase

VEGF:

Vascular endothelial growth factor

TGF-β:

Transforming growth factor-β

HGF:

Hepatocyte growth factor

SDF1:

Stromal-cell-derived factor 1

TIMP:

Tissue inhibitors of MMP

MAP:

Mitogen-activated protein

PyMT:

Polyoma middle T

EGF:

Epidermal growth factor

EGFR:

Epidermal growth factor receptor

COX-2:

Cyclooxygenase-2

uPA:

Urokinase plasminogen activator

CSF-1:

Colony stimulating factor 1

LLC:

Lewis lung carcinoma

TNF-α:

Tumor-necrosis factor-α

TLR:

Toll-like receptor

Tregs:

Regulatory T cells

PGE2:

Prostaglandin E2

SCF:

Stem cell factor

iNOS:

Nitric oxide synthase

ARG1:

Arginase 1

TCR:

T-cell receptor

NO:

Nitric oxide

ROS:

Reactive oxygen species

SAA3:

Serum amyloid A3

LOX:

Lysyl oxidase

FGF2:

Fibroblast growth factor-2

G-CSF:

Granulocyte colony stimulating factor

M-CSF:

Macrophage colony stimulating factor

FBLN5:

Fibulin-5

IFN:

Interferon

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Acknowledgments

We acknowledge European GRANT-FP7-Tumic HEALTH-F2-2008-201662 (MZ). Associazione Italiana per la Ricerca sul Cancro, AIRC (MZ) and Associazione Italiana per la Lotta al Neuroblastoma 2008–2010 (MZ), PRIN 2008 E5AZ5F (MZ). DS is supported by the Department of Biochemistry and Biotechnological Medicine, Università Federico II, Naples, Italy, and CEINGE, Centro di Ingegneria Genetica e Biotecnologie Avanzate, Naples, Italy.

Conflict of interest

The authors declare that they have no competing interests as defined by Clinical & Experimental Metastasis, or other interests that might be perceived as influencing the results and discussion reported in this manuscript.

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Authors and Affiliations

  1. Biotecnologie Avanzate, Centro di Ingegneria Genetica (CEINGE), Via Gaetano Salvatore 486, 80145, Naples, Italy

    Daniela Spano & Massimo Zollo

  2. Dipartimento di Biochimica e Biotecnologie Mediche, “Federico II” University of Naples, Via Sergio Pansini 5, 80131, Naples, Italy

    Daniela Spano & Massimo Zollo

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  1. Daniela Spano
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  2. Massimo Zollo
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Correspondence to Massimo Zollo.

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Spano, D., Zollo, M. Tumor microenvironment: a main actor in the metastasis process. Clin Exp Metastasis 29, 381–395 (2012). https://doi.org/10.1007/s10585-012-9457-5

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  • DOI: https://doi.org/10.1007/s10585-012-9457-5

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