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.
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.
Yoshizaki
Ayumi
A
Department of Tumor and Diagnostic Pathology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Nakayama
Toshiyuki
T
Yamazumi
Kazuyuki
K
Yakata
Yuichi
Y
Taba
Mitsuru
M
Sekine
Ichiro
I
D000230:Adenocarcinoma / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D002633:Chemotaxis; D015179:Colorectal Neoplasms / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D003593:Cytoplasm / Q000737:chemistry; D004789:Enzyme Activation; D006801:Humans; D007150:Immunohistochemistry; D017370:Interleukin-11 / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology; D008198:Lymph Nodes / Q000473:pathology; D019950:Mitogen-Activated Protein Kinase 1 / Q000187:drug effects / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000187:drug effects / Q000378:metabolism; D009361:Neoplasm Invasiveness; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects / Q000378:metabolism; D053702:Receptors, Interleukin-11 / Q000032:analysis / Q000378:metabolism*; D015854:Up-Regulation
D017370:Interleukin-11; D053702:Receptors, Interleukin-11; D019869:Phosphatidylinositol 3-Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3