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The Metastatic Process: An Overview

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Metastasis of Colorectal Cancer

Part of the book series: Cancer Metastasis - Biology and Treatment ((CMBT,volume 14))

Abstract

About one third of patients who will receive a cancer diagnostic will die of this disease. In most cases, death results from the formation of secondary neoplasms called metastases. The metastatic process is characterized by the detachment of cancer cells from the primary sites followed by their dissemination throughout the bloodstream and/or lymph stream to distal sites where they proliferate to give rise to secondary tumours. Intriguingly, the metastatic process is rather inefficient and in spite of its clinical significance, it remains poorly understood. Nevertheless, significant progress has been achieved during the past years and the increasing knowledge of the metastatic process is encouraging and raises high therapeutic expectations. Several events that lead to cancer and metastasis are under genetic and epigenetic controls. In particular, cancer initiation is tightly associated with specific mutations that affect proto-oncogenes and tumour suppressor genes. These mutations lead to unrestrained growth of the primary neoplasm and to a propensity to detach and progress through the subsequent steps of metastatic dissemination. Epigenetic alterations are mainly characterized by deregulation of DNA methylation and microRNA (miRNA)-dependent functions, as well as disruption of histone modifiers and chromatin-remodelling factors. In addition to these molecular alterations, several studies highlight that tumour development and dissemination rely on a continuous crosstalk between cancer cells and their microenvironments. This chapter will provide an overview of the metastatic process as it applies to colorectal cancer.

Nicolas Porquet and Stéphanie Gout contributed equally to this review

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Abbreviations

ADAM:

A disintegrin and metalloproteinase

Akt:

v-akt murine thymoma viral oncogene homologue 1

BDMC:

Bone marrow-derived cells

bFGF:

Basic fibroblast growth factor

BM:

Basement membrane

CAFs:

Cancer-associated fibroblasts

COX2:

Cyclooxygenase 2

CpG:

Cytosine-phosphate-guanine

CXC:

Chemokine C-X-C motif

CXCL:

Chemokine ligand

CXCR:

Chemokine C-X-C motif receptor

DR3:

Death receptor-3

ECM:

Extracellular matrix

EGFR:

Epidermal growth factor receptor

EMT:

Epithelial mesenchymal transition

EpCAM:

Epithelial cell adhesion molecule

ERK:

Extracellular-signal regulated kinase

eNOS:

Endothelial nitric oxide synthase

FAK:

Focal adhesion kinase

HGF:

Hepatocyte growth factor

HIF1α:

Hypoxia-inducible factor-1α

ICAM-1:

Intercellular adhesion molecule-1

IGF1/2:

Insulin-like growth factor-1/2

IL-3:

Interleukin-3

MAPK:

Mitogen-activated protein kinase

MACC1:

Metastasis-associated colon cancer 1

MET:

Mesenchymal-epithelial transition

miRNA:

microRNA

MMP:

Matrix metalloprotease

NK cells:

Natural killer cells

PCC:

Premature chromosome condensation

PDGFR:

Platelet-derived growth factor receptor

PI3K:

Phosphatidyl inositol 3 kinase

PLGF:

Placental growth factor

PTEN:

Phosphatase and tensin homolog deleted on chromosome 10

p38 MAPK:

p38 mitogen-activated protein kinase

ROS:

Reactive oxygen species

TAMs:

Tumour-associated macrophages

TIMP:

Tissue inhibitors of metalloprotease

TGFα:

Transforming growth factor-α

uPA:

Urokinase plasminogen activator

uPAR:

uPA receptor

VCAM:

Vascular cell adhesion molecule

VEGF:

Vascular endothelial cell growth factor

VEGFR:

Vascular endothelial cell growth factor receptor

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Acknowledgements

The work described in this chapter was supported by the Canadian Cancer Society Research Institute.

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Authors and Affiliations

  1. Le Centre de recherche en cancérologie de l’Université Laval et Centre de recherche du CHUQ, l’Hôtel-Dieu de Québec, Québec, QC, Canada, G1R 2J6

    Nicolas Porquet & Jacques Huot

  2. Institut Albert Bonniot Grenoble, Centre de recherche Inserm/UJF U823 Equipe 2, Grenoble, France

    Stéphanie Gout

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  1. Nicolas Porquet
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Correspondence to Nicolas Porquet .

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  1. Rosalind & Morris Goodman Cancer, Research Centre, McGill University, Promenade Sir William Osler 3655, Montreal, H3G 1Y6, Canada

    Nicole Beauchemin

  2. Hôpital L’Hôtel-Dieu de Québec, Centre de Recherche en Cancérologie, Université Laval, rue McMahon 9, Quebec, G1R 2J6, Canada

    Jacques Huot

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Porquet, N., Gout, S., Huot, J. (2010). The Metastatic Process: An Overview. In: Beauchemin, N., Huot, J. (eds) Metastasis of Colorectal Cancer. Cancer Metastasis - Biology and Treatment, vol 14. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-8833-8_1

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