Interleukin 7 upregulates vascular endothelial growth factor D in breast cancer cells and induces lymphangiogenesis in vivo.
BACKGROUND
Interleukin (IL) 7 is known to stimulate growth of breast cancer cells in vitro. It has been recently associated with node-positive tumours and with poor survival in breast cancer. The effects of IL-7 on the lymphangiogenic properties of breast cancer cells were explored.


METHODS
The effects of IL-7 on the expression of vascular endothelial growth factors (VEGFs) in MDA MB-231, MCF-7 and BT-483 cells were analysed by reverse transcriptase-polymerase chain reaction and western blotting. An in vivo lymphangiogenesis model using nude mice was developed. The newly generated microtubules were stained with anti-von Willebrand factor and anti-LYVE-1 (lymphatic vessel endothelial hyaluronan receptor) antibodies.


RESULTS
All VEGFs (VEGF-A, -B, -C and -D) were expressed in breast cancer cells, but at different levels. IL-7 increased the expression of VEGF-D at both mRNA and protein levels in MCF-7 and MDA MB-231 cells. In the in vivo model, IL-7 significantly induced the formation of lymphatic LYVE-1-positive, but not vascular von Willebrand factor-positive, microtubules (P = 0.021 versus sections without IL-7).


CONCLUSIONS
IL-7 induced the lymphangiogenic properties of breast cancer cells, probably by upregulation of VEGF-D. This might have a significant impact on the lymphatic spread of breast cancer.
Al-Rawi
M A A
MA
Metastasis and Angiogenesis Research Group, University Department of Surgery, University of Wales College of Medicine, Cardiff CF14 4XN, Wales, UK. mahir.al-rawi@doctors.org.uk
Watkins
G
G
Mansel
R E
RE
Jiang
W G
WG
D000818:Animals; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor / Q000187:drug effects; D005260:Female; D006801:Humans; D015851:Interleukin-7 / Q000494:pharmacology*; D042583:Lymphangiogenesis / Q000502:physiology*; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000378:metabolism*; D009368:Neoplasm Transplantation; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015854:Up-Regulation; D042643:Vascular Endothelial Growth Factor D / Q000378:metabolism*
D015851:Interleukin-7; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D042643:Vascular Endothelial Growth Factor D