Expression of interleukin-11 (IL-11) and IL-11 receptor alpha in human gastric carcinoma and IL-11 upregulates the invasive activity of human gastric carcinoma cells.
Previous investigations have shown that interleukin-11 (IL-11) and the IL-11 receptor (IL-11R) have been correlated with the regulation of tumor progression, cellular growth and differentiation in several malignant tumors. The objectives of this study were to clarify the role of IL-11 and IL-11Ralpha in human gastric carcinoma. IL-11 and IL-11Ralpha were studied in 73 cases of surgically resected human gastric adenocarcinomas by immunohistochemistry. The invasive activity and cell signaling pathway of gastric carcinoma cell lines were also examined. Among the 73 cases of adenocarcinoma, 53 (72.6%) and 47 cases (64.4%) showed positive staining in carcinoma cells for the IL-11 and IL-11Ralpha proteins, respectively. Histologically, IL-11 expression correlated only with Lauren's classification (p<0.05). The expression of IL-11Ralpha correlated with the grade of tumor invasion (p<0.05) and vessel infiltration (p<0.01). All of the four gastric carcinoma cell lines expressed both IL-11 and IL-11Ralpha proteins in western blot analysis. Recombinant human IL-11 (rhIL-11) promoted the migration of SCH cells by the activation of the phosphatidylinositol-3 kinase pathway. Wortmannin diminished the promotion of chemotactic motility and invasive activity by rhIL-11. These findings suggest that the IL-11/IL-11R pathway plays an important role in the progression and the differentiation of human gastric carcinomas.
Nakayama
Toshiyuki
T
Department of Tumor and Diagnostic Pathology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523, Japan. toshi-n@nagasaki-u.ac.jp
Yoshizaki
Ayumi
A
Izumida
Seiya
S
Suehiro
Tomoyuki
T
Miura
Shiro
S
Uemura
Takashi
T
Yakata
Yuichi
Y
Shichijo
Kazuko
K
Yamashita
Shunichi
S
Sekin
Ichiro
I
D000230:Adenocarcinoma / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D000730:Androstadienes / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects; D050822:Cytokine Receptor gp130 / Q000032:analysis / Q000378:metabolism; D006801:Humans; D017370:Interleukin-11 / Q000032:analysis / Q000378:metabolism*; D053703:Interleukin-11 Receptor alpha Subunit / Q000032:analysis / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D011994:Recombinant Proteins / Q000494:pharmacology; D013274:Stomach Neoplasms / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D015854:Up-Regulation; D000077191:Wortmannin
D000730:Androstadienes; C494199:IL6ST protein, human; D017370:Interleukin-11; D053703:Interleukin-11 Receptor alpha Subunit; D011994:Recombinant Proteins; D050822:Cytokine Receptor gp130; D019869:Phosphatidylinositol 3-Kinases; D000077191:Wortmannin