IL-1α Secreted by Colon Cancer Cells Enhances Angiogenesis: The Relationship Between IL-1α Release and Tumor Cells' Potential for Liver Metastasis

Background and Objectives: Interleukin (IL)-1 alpha plays an important role in colon cancer progression and angiogenesis. We here asked whether IL-1 alpha derived from cancer cells modulates vascular endothelial cell growth, migration and tubule formation. Methods: The existence of IL-1 alpha mRNA and protein in colon cancer cell lines (WiDr, Ht-29, Caco-2, COLO 320) were investigated with RT-PCR and ELISA. Proliferation and invasion were investigated by MTS assay and Matrigel-double chamber assay. To answer our main question, we performed angiogenesis assay used an in vitro model consisting of co-cultivated tumor cells and stromal cells. Results: IL-1 alpha mRNA and protein were detected in highly metastatic colon cancer cells, (WiDr and HT-29). Recombinant IL-1 alpha significantly enhanced growth and invasiveness of human umbilical vein endothelial cells (HUVEC) (P < 0.01). Moreover, HUVEC growth and migration were significantly enhanced by WiDr compared to control (without co-culture) or CAco-2 (P < 0.05). Exogenous rIL-1 alpha significantly enhanced HUVEC tube-like formation in a dose-dependent manner (P < 0.01) in a HUVEC/fibroblast co-cultivation system. Moreover, WiDr significantly enhanced HUVEC tubule formation compared with control of CAco-2 (P < 0.01). Conclusion: Based on these findings, we conclude that colon cancer cell-derived IL-1 alpha up-regulates angiogenesis by modulating stromal cells within the tumor cells' microenvironment.