Interleukin 7 upregulates vascular endothelial growth factor D in breast cancer cells and induces lymphangiogenesis in vivo.

Abstract

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. 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. 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). 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.