Interleukin-8 is associated with proliferation, migration, angiogenesis and chemosensitivity in vitro and in vivo in colon cancer cell line models

Yan Ning, Philipp C Manegold, Young Kwon Hong, Wu Zhang, Alexandra Pohl, Georg Lurje, Thomas Winder, Dongyun Yang, Melissa J LaBonte, Peter M Wilson, Robert D Ladner, Heinz-Josef Lenz, Melissa LaBonte Wilson

Research output: Contribution to journalArticle

274 Citations (Scopus)

Abstract

Interleukin-8 (IL-8), a chemokine with a defining CXC amino acid motif, is known to possess tumorigenic and proangiogenic properties. Overexpression of IL-8 has been detected in many human tumors, including colorectal cancer (CRC), and is associated with poor prognosis. The goal of our study was to determine the role of IL-8 overexpression in CRC cells in vitro and in vivo. We stably transfected the IL-8 cDNA into two human colon cancer cell lines, HCT116 and Caco2, and selected IL-8-secreting transfectants. Real-time RT-PCR confirmed that IL-8 mRNA was overexpressed in IL-8 transfectants with 45- to 85-fold higher than parental cells. The IL-8-transfected clones secreted 19- to 28-fold more IL-8 protein than control and parental cells as detected by ELISA. The IL-8 transfectants demonstrated increased cellular proliferation, cell migration and invasion based on functional assays. Growth inhibition studies showed that IL-8 overexpression lead to a significant resistance to oxaliplatin (p < 0.0001). Inhibition of IL-8 overexpression with small interfering RNA reversed the observed increases in tumorigenic functions and oxaliplatin resistance, suggesting that IL-8 not only provides a proliferative advantage but also promotes the metastatic potential of colon cancer cells. Using a tumor xenograft model, IL-8-expressing cells formed significantly larger tumors than the control cells with increased microvessel density. Together, these findings indicate that overexpression of IL-8 promotes tumor growth, metastasis, chemoresistance and angiogenesis, implying IL-8 to be an important therapeutic target in CRC.

Original languageEnglish
Pages (from-to)2038-49
Number of pages12
JournalInternational journal of cancer. Journal international du cancer
Volume128
Issue number9
DOIs
Publication statusPublished - 01 May 2011

Bibliographical note

Copyright © 2010 UICC.

Keywords

  • Animals
  • Blotting, Western
  • Caco-2 Cells
  • Cell Movement
  • Cell Proliferation
  • Colonic Neoplasms
  • Drug Resistance, Neoplasm
  • Enzyme-Linked Immunosorbent Assay
  • HCT116 Cells
  • Humans
  • Immunohistochemistry
  • Interleukin-8
  • Mice
  • Neovascularization, Pathologic
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transfection
  • Xenograft Model Antitumor Assays

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