Interleukin-15 Expression Is Associated with Malignant Potential in Colon Cancer CellsKuniyasu H.a · Oue N.b · Nakae D.a · Tsutsumi M.a · Denda A.a · Tsujiuchi T.a · Yokozaki H.b · Yasui W.b
aDepartment of Oncological Pathology, Cancer Center, Nara Medical University, Kashihara, and bFirst Department of Pathology, Hiroshima University School of Medicine, Hiroshima, Japan
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Interleukin 15 (IL-15 mRNA expression was detected in human colorectal cancer cells (Colo320, WiDr, TCO and DLD1) by the reverse transcriptase-polymerase chain reaction (RT-PCR). Only Colo320 and WiDr cells secreted IL-15 culture medium. With IL-15 treatment, all cell lines grew at a rate of 120–180% of that of nontreated cells. A binding assay with 125I-labeled IL-15 showed binding activity to IL-15 in Colo320 (Kd: 0.098 nM) cells. IL-15 also reversed the growth inhibition caused by serum starvation in Colo320 cells. IL-15-induced cell growth in regular and serum-free media was abrogated by anti-IL-15 antibody treatment in Colo320 cells. Moreover, IL-15 treatment reduced doxorubicin-induced cytostasis and cytolysis in Colo320 cells by 50%. The invasion capacity of IL-15-treated Colo320 cells was 5.3 times that of untreated cells. Immunoblotting showed that IL-15-treated Colo320 cells exhibited downregulation of p21Waf1 and Bax, and upregulation of Bcl-2, phospho-AKT, MMP9/MMP2, and VEGF. Finally, immunostaining of human colon cancer revealed that 33 (70%) of 47 Dukes’ C cases showed IL-15 expression in cancer cells, whereas only 16% of Dukes’ B cases did (p < 0.0001). IL-15 may play important roles in cell proliferation, invasion, and metastasis of human colorectal cancer.
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