Expression of interleukin (IL)-11 and IL-11 receptor in human colorectal adenocarcinoma : IL-11 up-regulation of the invasive and proliferative activity of human colorectal carcinoma cells

• Published in: International journal of oncology Vol. 29; no. 4; pp. 869 - 876
• Main Authors: YOSHIZAKI, Ayumi, NAKAYAMA, Toshiyuki, YAMAZUMI, Kazuyuki, YAKATA, Yuichi, TABA, Mitsuru, SEKINE, Ichiro
• Format: Journal Article
• Language: English
• Published: Athens Editorial Academy of the International Journal of Oncology 01.10.2006
• Subjects: Adenocarcinoma - chemistry; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Biological and medical sciences; Cell Proliferation; Cells, Cultured; Chemotaxis; Colorectal Neoplasms - chemistry; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Cytoplasm - chemistry; Enzyme Activation; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Immunohistochemistry; Interleukin-11 - analysis; Interleukin-11 - metabolism; Interleukin-11 - pharmacology; Lymph Nodes - pathology; Medical sciences; Mitogen-Activated Protein Kinase 1 - drug effects; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - drug effects; Mitogen-Activated Protein Kinase 3 - metabolism; Neoplasm Invasiveness; Phosphatidylinositol 3-Kinases - drug effects; Phosphatidylinositol 3-Kinases - metabolism; Receptors, Interleukin-11 - analysis; Receptors, Interleukin-11 - metabolism; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors; Up-Regulation; Human; IL-11 receptor; Rectal disease; Enzyme; PI3 kinase; Transferases; Colorectal adenocarcinoma; Colorectal carcinoma; Colorectal cancer; Cytokine; Interleukin 11; Mitogen-activated protein kinase; MAP kinase; Malignant tumor; IL-11; Biological activity; 1-Phosphatidylinositol 3-kinase; Colonic disease; Colon cancer; Cancerology; Digestive diseases; Intestinal disease; Biological receptor
• ISSN: 1019-6439; 1791-2423
• DOI: 10.3892/ijo.29.4.869

Previous investigations have shown that interleukin (IL)-11/IL-11 receptor alpha-chain (IL-11Ralpha), a member of the PI3K, MAPK and JAK-STAT activating family of cytokines/receptors, correlates with the regulation of tumor progression. In this study, we established the IL-11/IL-11Ralpha expression profile in human colorectal adenocarcinoma (CRC) and clarified its signaling pathway and role in the invasion activity of CRC cell lines. To elucidate the role of IL-11/IL-11Ralpha, we examined 103 cases of CRC and 24 cases of colorectal adenoma by immunohistochemistry. In addition, we investigated the invasive activity of cell signaling pathway of CRC cell lines. The IL-11Ralpha expression was correlated with tumor invasion and lymphatic infiltration (p<0.01, respectively). Recombinant human IL-11 (rhIL-11) promoted the migration and proliferation of HT-29 cells and activated the PI3K and p44/p42 MAPK pathways. Wortmannin, a PI3K inhibitor, and PD98059, a p44/p42 MAPK inhibitor, significantly reduced the promotion of invasion and proliferation activity by rhIL-11, respectively. In summary, the IL-11Ralpha expression was correlated with clinicopathological features and IL-11 promoted the invasion via the PI3K and up-regulated the proliferation via the p44/p42 MAPK in CRC cells. These findings suggested that the IL-11/IL-11R pathway plays an important role in the progression of CRC.