Clinical & Experimental Metastasis

, Volume 29, Issue 4, pp 381–395 | Cite as

Tumor microenvironment: a main actor in the metastasis process

  • Daniela Spano
  • Massimo ZolloEmail author


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.


Tumor microenvironment Immune inflammatory cells Cancer-associated fibroblasts Hierarchic network of communication 



Extracellular matrix


Cancer-associated fibroblasts


Major histocompatibility complex


Tumor-associated macrophages


Myeloid-derived suppressor cells


Tenascin C


Monocyte chemotactic protein 1




Matrix metalloproteinase


Vascular endothelial growth factor


Transforming growth factor-β


Hepatocyte growth factor


Stromal-cell-derived factor 1


Tissue inhibitors of MMP


Mitogen-activated protein


Polyoma middle T


Epidermal growth factor


Epidermal growth factor receptor




Urokinase plasminogen activator


Colony stimulating factor 1


Lewis lung carcinoma


Tumor-necrosis factor-α


Toll-like receptor


Regulatory T cells


Prostaglandin E2


Stem cell factor


Nitric oxide synthase


Arginase 1


T-cell receptor


Nitric oxide


Reactive oxygen species


Serum amyloid A3


Lysyl oxidase


Fibroblast growth factor-2


Granulocyte colony stimulating factor


Macrophage colony stimulating factor







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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© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  1. 1.Biotecnologie AvanzateCentro di Ingegneria Genetica (CEINGE)NaplesItaly
  2. 2.Dipartimento di Biochimica e Biotecnologie Mediche“Federico II” University of NaplesNaplesItaly

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