Interleukin-8 is associated with proliferation, migration, angiogenesis and chemosensitivity in vitro and in vivo in colon cancer cell line models
Data(s) |
01/05/2011
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Resumo |
<p>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.</p> |
Identificador | |
Idioma(s) |
eng |
Direitos |
info:eu-repo/semantics/restrictedAccess |
Fonte |
Ning , Y , Manegold , P C , Hong , Y K , Zhang , W , Pohl , A , Lurje , G , Winder , T , Yang , D , LaBonte , M J , Wilson , P M , Ladner , R D , Lenz , H-J & LaBonte Wilson , M 2011 , ' Interleukin-8 is associated with proliferation, migration, angiogenesis and chemosensitivity in vitro and in vivo in colon cancer cell line models ' International journal of cancer. Journal international du cancer , vol 128 , no. 9 , pp. 2038-49 . DOI: 10.1002/ijc.25562 |
Palavras-Chave | #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 |
Tipo |
article |