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IL‐1α secreted by colon cancer cells enhances angiogenesis: The relationship between IL‐1α release and tumor cells' potential for liver metastasis
Author(s) -
Matsuo Yoichi,
Sawai Hirozumi,
Ma Jiachi,
Xu Donghui,
Ochi Nobuo,
Yasuda Akira,
Takahashi Hiroki,
Funahashi Hitoshi,
Takeyama Hiromitsu
Publication year - 2009
Publication title -
journal of surgical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.201
H-Index - 111
eISSN - 1096-9098
pISSN - 0022-4790
DOI - 10.1002/jso.21245
Subject(s) - angiogenesis , matrigel , stromal cell , metastasis , cancer research , umbilical vein , medicine , colorectal cancer , cancer cell , gentamicin protection assay , tumor microenvironment , human umbilical vein endothelial cell , cancer , biology , in vitro , biochemistry , tumor cells
Background and Objectives Interleukin (IL)‐1α plays an important role in colon cancer progression and angiogenesis. We here asked whether IL‐1α derived from cancer cells modulates vascular endothelial cell growth, migration and tubule formation. Methods The existence of IL‐1α 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‐1α mRNA and protein were detected in highly metastatic colon cancer cells (WiDr and HT‐29). Recombinant IL‐1α 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‐1α 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 or Caco‐2 ( P < 0.01). Conclusion Based on these findings, we conclude that colon cancer cell‐derived IL‐1α up‐regulates angiogenesis by modulating stromal cells within the tumor cells' microenvironment. J. Surg. Oncol. 2009;99:361–367. © 2009 Wiley‐Liss, Inc.