IL-1alpha secreted by colon cancer cells enhances angiogenesis: the relationship between IL-1alpha release and tumor cells' potential for liver metastasis.
OBJECTIVE
Interleukin (IL)-1alpha plays an important role in colon cancer progression and angiogenesis. We here asked whether IL-1alpha derived from cancer cells modulates vascular endothelial cell growth, migration and tubule formation.


METHODS
The existence of IL-1alpha 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-1alpha mRNA and protein were detected in highly metastatic colon cancer cells (WiDr and HT-29). Recombinant IL-1alpha 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-1alpha 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).


CONCLUSIONS
Based on these findings, we conclude that colon cancer cell-derived IL-1alpha up-regulates angiogenesis by modulating stromal cells within the tumor cells' microenvironment.
Matsuo
Yoichi
Y
Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya 4678601, Japan.
Sawai
Hirozumi
H
Ma
Jiachi
J
Xu
Donghui
D
Ochi
Nobuo
N
Yasuda
Akira
A
Takahashi
Hiroki
H
Funahashi
Hitoshi
H
Takeyama
Hiromitsu
H
D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D053582:Interleukin-1alpha / Q000235:genetics / Q000378:metabolism*; D008113:Liver Neoplasms / Q000098:blood supply* / Q000556:secondary*; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D053582:Interleukin-1alpha; D012333:RNA, Messenger