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Pivotal Role of Pervasive Neoplastic and Stromal Cells Reprogramming in Circulating Tumor Cells Dissemination and Metastatic Colonization

  • Review Paper
  • Published:
Cancer Microenvironment

Abstract

Reciprocal interactions between neoplastic cells and their microenvironment are crucial events in carcinogenesis and tumor progression. Pervasive stromal reprogramming and remodeling that transform a normal to a tumorigenic microenvironment modify numerous stromal cells functions, status redox, oxidative stress, pH, ECM stiffness and energy metabolism. These environmental factors allow selection of more aggressive cancer cells that develop important adaptive strategies. Subpopulations of cancer cells acquire new properties associating plasticity, stem-like phenotype, unfolded protein response, metabolic reprogramming and autophagy, production of exosomes, survival to anoikis, invasion, immunosuppression and therapeutic resistance. Moreover, by inducing vascular transdifferentiation of cancer cells and recruiting endothelial cells and pericytes, the tumorigenic microenvironment induces development of tumor-associated vessels that allow invasive cells to gain access to the tumor vessels and to intravasate. Circulating cancer cells can survive in the blood stream by interacting with the intravascular microenvironment, extravasate through the microvasculature and interact with the metastatic microenvironment of target organs. In this review, we will focus on many recent paradigms involved in the field of tumor progression.

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Abbreviations

COX2:

Cyclooxygenase 2

PDGF:

Release platelet-derived growth factor

PDGFR:

Release platelet-derived growth factor receptor

NF-κB:

Nuclear factor kappa-light-chain-enhancer of activated B cells

HIF-1:

Hypoxia-inducible factor 1

HGF:

Hepatocyte growth factor

VEGF:

Vascular endothelial growth factor

FSP-1:

Fibroblast-specific protein 1

SDF-1:

Stromal cell-derived factor 1

EGFR:

Epidermal growth factor receptor

RANKL:

Receptor activator of nuclear factor kappa-B ligand

TGF-β:

Transforming growth factor beta

FGF:

Fibroblast growth factors

IFNs:

Interferons

TNF1α:

Tumor necrosis factor 1 Alpha

LOX:

Lysyl oxidase

MCT1:

Monocarboxylate transporter 1

MCT4:

Monocarboxylate transporter 4

Shh:

Sonic Hedgehog

LC3:

Microtubule-associated protein 1 light chain 3

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Acknowledgements

This work was supported by grant INCa-DGOS-4654.

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The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Platform of Investigative Pathology and Department of Biopathology, Curie Institute, 26 rue d’Ulm, 75248, Paris, Cedex 05, France

    Didier Meseure

  2. Laboratory of Investigative Pathology and Department of Tumors Biopathology, Institute Curie, 26 rue d’Ulm, 75248, Paris, Cedex 05, France

    Kinan Drak Alsibai & Andre Nicolas

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  1. Didier Meseure
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  2. Kinan Drak Alsibai
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Correspondence to Didier Meseure.

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Meseure, D., Drak Alsibai, K. & Nicolas, A. Pivotal Role of Pervasive Neoplastic and Stromal Cells Reprogramming in Circulating Tumor Cells Dissemination and Metastatic Colonization. Cancer Microenvironment 7, 95–115 (2014). https://doi.org/10.1007/s12307-014-0158-2

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