Clinical & Experimental Metastasis

, Volume 24, Issue 8, pp 619–636

Lymphatic metastasis in breast cancer: importance and new insights into cellular and molecular mechanisms

Research Paper

Abstract

Lymph node metastasis is the main prognosis factor in a number of malignancies, including breast carcinomas. The means by which lymph node metastases arise is not fully understood, and many questions remain about their importance in the further spread of breast cancer. Nevertheless, a number of key cellular and molecular mechanisms of lymphatic metastasis have been identified. These include induction of intra- or peri-tumoral lymphangiogenesis or co-option of existing lymphatic vessels to allow tumour cells to enter the lymphatics, although it remains to be established whether this is primarily an active or passive process. Gene expression microarrays and functional studies in vitro and in vivo, together with detailed clinical observations have identified a number of molecules that can play a role in the genesis of lymph node metastases. These include the well-recognised lymphangiogenic cytokines VEGF-C and VEGF-D as well as chemokine-receptor interactions, integrins and downstream signalling pathways. This paper briefly reviews current clinical and experimental evidence for the underlying mechanisms and significance of lymphatic metastasis in breast cancer and highlights questions that still need to be addressed.

Keywords

Lymph node Metastasis Breast cancer Lymphangiogenesis Chemokines 

Abbreviations

Primary

Secondary

BVI

Blood vessel invasion

CAM

Cell adhesion molecule

DCIS

Ductal carcinoma in situ

DFS

Disease-free survival

ER

Oestrogen receptor

FAK

Focal adhesion kinase

HIF

Hypoxia inducible factor

IGF-1R

Insulin-like growth factor 1 receptor

IGFBP

Insulin-like growth factor binding protein

IHC

Immunohistochemistry

ILK

Integrin-linked kinase

LEC

Lymphatic endothelial cell

LN(M)

Lymph node (metastasis)

LVD

Lymphatic vessel density

LVI

Lymphovascular invasion

MMP

Matrix metalloprotease

MVD

Microvessel density

NO(S)

Nitric oxide synthase

NSAID

Non-steroidal anti-inflammatory drug

NSCLC

Non-small cell lung cancer

OS

Overall survival

PAX5

Paired box gene 5

RTK(i)

Receptor tyrosine kinase (inhibitor)

SCC(HN)

Squamous cell carcinoma (of the head and neck)

SLN

Sentinel lymph node

TAM

Tumour associated macrophage

uPAR

Urokinase plasminogen activator receptor

VEGF(R)

Vascular endothelial growth factor (receptor)

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Copyright information

© Springer Science+Business Media B.V. 2007

Authors and Affiliations

  1. 1.Cancer Research UK Centre for Cancer Therapeutics, McElwain LaboratoriesThe Institute of Cancer ResearchSurreyUK
  2. 2.Forschungszentrum Karlsruhe, Institut für Toxikologie und GenetikKarlsruheGermany

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