Interleukin-1alpha enhances angiogenesis and is associated with liver metastatic potential in human gastric cancer cell lines.
BACKGROUND
To better understand the underlying mechanism of liver metastasis formation in human gastric cancer, we evaluated the angiogenic capabilities of human gastric cancer cell lines with different metastatic potentials as well as the role of interleukin (IL)-1alpha in the angiogenic process.


METHODS
Reverse transcription-polymerase chain reaction was used to detect the expression of IL-1alpha and vascular endothelial growth factor (VEGF) mRNA in gastric cancer cell lines with different liver metastatic potentials. Levels of VEGF secreted by human gastric cancer cells were measured by enzyme-linked immunosorbent assay. We also examined how gastric cancer cells with different metastatic potentials influence the proliferation and tube formation of human umbilical vein endothelial cells (HUVECs) using the Premix WST-1 cell proliferation assay system and an angiogenesis assay, respectively.


RESULTS
IL-1alpha expression levels were significantly correlated with liver metastatic potential in gastric cancer cell lines. Levels of VEGF secreted by gastric cancer cells appear to be regulated by IL-1alpha through IL-1 receptor Type 1 and were correlated with liver metastatic potential. Both HUVEC proliferation and tube formation were strongly enhanced by coculture with high liver-metastatic gastric cancer cells and were enhanced to a similar extent by culture in the presence of IL-1alpha. In contrast, blockade of IL-1alpha inhibited both HUVEC proliferation and angiogenesis.


CONCLUSIONS
IL-1alpha may play a role in liver metastasis of gastric cancer via enhanced vascular endothelial cell proliferation and angiogenesis.
Ma
Jiachi
J
Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Sawai
Hirozumi
H
Matsuo
Yoichi
Y
Ochi
Nobuo
N
Yasuda
Akira
A
Takahashi
Hiroki
H
Wakasugi
Takehiro
T
Funahashi
Hitoshi
H
Sato
Mikinori
M
Okada
Yuji
Y
Takeyama
Hiromitsu
H
Manabe
Tadao
T
D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018920:Coculture Techniques; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D006801:Humans; D053582:Interleukin-1alpha / Q000502:physiology*; D008113:Liver Neoplasms / Q000556:secondary*; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D012333:RNA, Messenger / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D013274:Stomach Neoplasms / Q000098:blood supply* / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D053582:Interleukin-1alpha; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D042461:Vascular Endothelial Growth Factor A