Interleukin-15 expression is associated with malignant potential in colon cancer cells

Pathobiology. 2001;69(2):86-95. doi: 10.1159/000048761.


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 (125)I-labeled IL-15 showed binding activity to IL-15 in Colo320 (K(d): 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Animals
  • Binding Sites
  • Cell Division / drug effects
  • Cell Survival / drug effects
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Culture Media, Serum-Free
  • Dose-Response Relationship, Drug
  • Doxorubicin / pharmacology
  • Drug Antagonism
  • Gene Expression Regulation / drug effects
  • Interleukin-15 / genetics*
  • Interleukin-15 / metabolism
  • Neoplasm Invasiveness
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • RNA, Messenger / metabolism
  • RNA, Neoplasm / analysis
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured / drug effects


  • Culture Media, Serum-Free
  • Interleukin-15
  • Neoplasm Proteins
  • RNA, Messenger
  • RNA, Neoplasm
  • Doxorubicin