Interleukin-8 is associated with proliferation, migration, angiogenesis and chemosensitivity in vitro and in vivo in colon cancer cell line models.
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.
Ning
Yan
Y
Division of Medical Oncology, Sharon A. Carpenter Laboratory, University of Southern California/Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles, CA 90033, USA.
Manegold
Philipp C
PC
Hong
Young Kwon
YK
Zhang
Wu
W
Pohl
Alexandra
A
Lurje
Georg
G
Winder
Thomas
T
Yang
Dongyun
D
LaBonte
Melissa J
MJ
Wilson
Peter M
PM
Ladner
Robert D
RD
Lenz
Heinz-Josef
HJ
D000818:Animals; D015153:Blotting, Western; D018938:Caco-2 Cells; D002465:Cell Movement; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology*; D019008:Drug Resistance, Neoplasm / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D045325:HCT116 Cells; D006801:Humans; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000378:metabolism*; D051379:Mice; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
C508606:CXCL8 protein, human; D016209:Interleukin-8