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Angiogenesis and Lymphangiogenesis in Colon Cancer Metastasis

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Metastasis of Colorectal Cancer

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

Abstract

The vascular system markedly contributes to the pathogenesis of colorectal cancer (CRC). Indeed, agents targeting angiogenesis (bevacizumab) exhibit considerable efficacy in treatment of metastatic CRC, but less so in other (adjuvant) settings. These unexpected outcomes indicate that, to make further progress, a more complete understanding is required of the relationship between the tumour cell compartment and various facets of the vasculature. Here, we review the general mechanisms involved in angiogenesis and lymphangiogenesis during formation, growth and metastatic dissemination of CRC. We discuss several levels at which blood vessel growth is regulated, namely through local growth factor networks, circulating effectors, coagulation system, microvesicles and bone marrow-derived cells, the latter acting at the systemic level. We survey the mechanisms triggering the proangiogenic state in cancer, including microenvironment and oncogenic pathways, and discuss the developments in anti-angiogenic therapy.

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Abbreviations

Ang-2:

Angiopoietin-2

APC:

Adenomatous polyposis coli

ARNT:

Aryl hydrocarbon nuclear translocator

BECs:

Blood vessel endothelial cells

bFGF:

Basic fibroblast growth factor

BM:

Bone marrow

BMDCs:

Bone marrow-derived cells

CEPs:

Circulating endothelial progenitors

CNS:

Central nervous system

COX-2:

Cyclooxygenase2

CRC:

Colorectal cancer

CSCs:

Cancer stem cells

CSFs:

Colony stimulating factors

CXCR4:

Chemokine C-X-C motif receptor 4

Dll4-4:

Notch ligand, delta-like 4 (Dll-4)

EGF:

Epidermal growth factor

ECM:

Extracellular matrix

EPCs:

Endothelial progenitor cells

EPCR:

Endothelial protein C receptor

FGF:

Fibroblast growth factor

Flk-1:

Fetal liver kinase 1

Flt-1:

fms-related tyrosine kinase 1

Foxc2:

Forkhead box C2

GI:

Gastrointestinal

HGF:

Hepatocyte growth factor

HER-2:

Human epidermal growth factor receptor-2

HIF:

Hypoxia inducible factor

HPCs:

Hematopoietic progenitor cells

HSCs:

Hematopoietic stem cells

Id1:

DNA-binding protein inhibitor 1

IGF-1:

Insulin-like growth factor-1

IGF-1R:

Insulin-like growth factor-1 receptor

HRE:

Hypoxia responsive element

KDR:

Kinase insert domain-containing receptor

LDH:

Lactate dehydrogenase

LECs:

Lymphatic endothelial cells

LYVE-1:

Lymphatic vessel endothelial hyaluronan receptor 1

MMP:

Matrix metalloproteinase

MVD:

Microvessel density

NRP1:

Neuropilin 1

PARs:

Protease activated receptors

PDGF-B:

Platelet-derived growth factor B (PDGF-B)

PEDF:

Pigment epithelium-derived factor

PF4:

Platelet factor 4

PI3K:

Phosphatidyl inositol kinase 3

PLGF:

Placental growth factor

Prox-1:

Prospero homeobox transcription factor

SDF1:

Stromal-derived factor 1

sVEGFR:

Soluble splice isoforms of vascular endothelial growth factor receptor

TF:

Tissue factor

TICs:

Tumour initiating cells

Tie2/TEK:

Tyrosine kinase with immunoglobulin-like and EGF-like domains 2

TM:

Thrombomodulin

TSP:

Thrombospondin

TVI:

Tumour-vascular interface

UTR:

3’ untranslated region

VEGF:

Vascular endothelial growth factor

VEGFR2:

Vascular endothelial growth factor receptor 2

VHL:

Von Hippel Lindau

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Acknowledgments

This work was supported by operating grants to J.R. from the Canadian Cancer Society (CCS) and Team Grant from Canadian Institutes of Health Research. JR is a recipient of the Jack Cole Chair in Pediatric Oncology at McGill University. Infrastructure funds were contributed by Fonds de la recherche en santé du Québec (FRSQ). We thank our families, especially Françoise Garnier, Jean-Pierre Garnier, Anna Rak and Danuta Rak for their support and patience.

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    Delphine Garnier & Janusz Rak

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  1. Delphine Garnier
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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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Garnier, D., Rak, J. (2010). Angiogenesis and Lymphangiogenesis in Colon Cancer Metastasis. 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_9

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