Interleukin-1 receptor antagonist inhibits the expression of vascular endothelial growth factor in colorectal carcinoma.
OBJECTIVE
Interleukin (IL)-1 is known to act as a tumor growth factor by inducing angiogenic factors. We examined the significance of IL-1beta and IL-1 receptor antagonist (RA) for inducing the expression of vascular endothelial growth factor (VEGF) in colorectal cancers.


METHODS
We investigated the expression of VEGF induced by IL-1beta in five colon cancer cell lines and the possible involvement of IL-1 RA. We also measured the tissue concentrations of IL-1beta, IL-1 RA and VEGF by ELISA in 65 colorectal cancer patients.


RESULTS
IL-1beta induced VEGF secretion with a 19-fold increase in Caco-2 cells. A significant increase in VEGF secretion was also observed in SW480 and WiDr cells. IL-1 RA inhibited IL-1beta-induced VEGF secretion by 87%. Our data from the clinically obtained specimens showed that the IL-1 RA/IL-1beta ratio is significantly lower in cancer tissue. Regarding the clinicopathological parameters, the IL-1 RA/IL-1beta ratio was significantly lower in patients with vessel involvement than in those without involvement, and IL-1 RA/IL-1beta ratio was negatively correlated with the VEGF protein level in colorectal tumors.


CONCLUSIONS
Our data suggest that IL-1beta induces VEGF expression and IL-1 RA acts as the competitive inhibitor, and that the IL-1 RA/IL-1beta ratio is significant for VEGF expression in the microenvironment of colorectal cancer tissue. We conclude that IL-1beta induces VEGF secretion in a certain population of colorectal cancer patients, and that IL-1 RA is the potential therapeutic agent for antiangiogenic therapy in colorectal cancer patients.
Konishi
Naomi
N
Second Department of Surgery, Mie University School of Medicine, 2-174 Edobashi, Tsu, Japan.
Miki
Chikao
C
Yoshida
Toshimichi
T
Tanaka
Koji
K
Toiyama
Yuji
Y
Kusunoki
Masato
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002277:Carcinoma / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
D000970:Antineoplastic Agents; D007375:Interleukin-1; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D042461:Vascular Endothelial Growth Factor A