Induction of IL-8 and monocyte chemoattractant protein-1 by doxorubicin in human small cell lung carcinoma cells

Misako Shibakura, Kenji Niiya, Toru Kiguchi, Isao Kitajima, Masami Niiya, Noboru Asaumi, Nam ho Huh, Yasunari Nakata, Mine Harada, Mitsune Tanimoto

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Abstract

We previously demonstrated doxorubicin-induced urokinase expression in human H69 SCLC cells by the microarray technique using Human Cancer CHIP version 2 (Takara Shuzo, Kyoto, Japan), in which 425 human cancer-related genes were spotted on glass plates (Kiguchi et al., Int J Cancer 2001;93:792-7). Microarray analysis also revealed significant induction of IL-8, a member of the CXC chemokines. We have, therefore, extended the observation by testing the effects of doxorubicin on expression of the chemokine family and provide here definitive evidence that doxorubicin induces IL-8 and MCP-I, one of the CC chemokines, at least in 2 human SCLC cells, H69 and SBC-I. IL-8 antigen levels, measured by ELISA, were markedly increased in both H69 and SBC-I conditioned media after doxorubicin treatment, in parallel with mRNA levels; and this was dependent on the dose of doxorubicin. The ribonuclease protection assay, using a multiprobe template set for human chemokines, revealed induction of not only IL-8 but also MCP-I in doxorubicin-treated H69 cells. MCP-I antigen levels increased approximately 100-fold in doxorubicin-treated H69 cells. RT-PCR using specific primers for MCP-I suggested that doxorubicin also induced MCP-I expression in SBC-I and SBC-3 SCLC cells. Futhermore, CAT analysis using IL-8 promoter implicated the PEA3 transcriptional factor, whose binding site was located immediately upstream of the AP-I and NF-ΚB binding sites. Thus, it is suggested that doxorubicin induces IL-8 and MCP-I chemokines in human SCLC cells by activating gene expression, in which at least PEA3 is involved. IL-8 and MCP-I are major chemoattractants for neutrophils and monocytes/macrophages, respectively; therefore, extensive induction of IL-8 and MCP-I may provoke the interaction between inflammatory/immune cells and tumor cells under doxorubicin stimulation and influence many aspects of tumor cell biology.

Original languageEnglish
Pages (from-to)380-386
Number of pages7
JournalInternational Journal of Cancer
Volume103
Issue number3
DOIs
Publication statusPublished - Jan 20 2003

Fingerprint

Chemokine CCL2
Small Cell Lung Carcinoma
Interleukin-8
Doxorubicin
Chemokines
Neoplasms
Binding Sites
CXC Chemokines
CC Chemokines
Neoplasm Genes
Chemotactic Factors
Urokinase-Type Plasminogen Activator
Microarray Analysis
Ribonucleases
Conditioned Culture Medium
Glass
Cell Biology
Monocytes
Japan
Neutrophils

Keywords

  • Doxorubicin
  • IL-8
  • MCP-I
  • PEA3
  • Small cell lung carcinoma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Induction of IL-8 and monocyte chemoattractant protein-1 by doxorubicin in human small cell lung carcinoma cells. / Shibakura, Misako; Niiya, Kenji; Kiguchi, Toru; Kitajima, Isao; Niiya, Masami; Asaumi, Noboru; Huh, Nam ho; Nakata, Yasunari; Harada, Mine; Tanimoto, Mitsune.

In: International Journal of Cancer, Vol. 103, No. 3, 20.01.2003, p. 380-386.

Research output: Contribution to journalArticle

Shibakura, M, Niiya, K, Kiguchi, T, Kitajima, I, Niiya, M, Asaumi, N, Huh, NH, Nakata, Y, Harada, M & Tanimoto, M 2003, 'Induction of IL-8 and monocyte chemoattractant protein-1 by doxorubicin in human small cell lung carcinoma cells', International Journal of Cancer, vol. 103, no. 3, pp. 380-386. https://doi.org/10.1002/ijc.10842
Shibakura, Misako ; Niiya, Kenji ; Kiguchi, Toru ; Kitajima, Isao ; Niiya, Masami ; Asaumi, Noboru ; Huh, Nam ho ; Nakata, Yasunari ; Harada, Mine ; Tanimoto, Mitsune. / Induction of IL-8 and monocyte chemoattractant protein-1 by doxorubicin in human small cell lung carcinoma cells. In: International Journal of Cancer. 2003 ; Vol. 103, No. 3. pp. 380-386.
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AU - Kitajima, Isao

AU - Niiya, Masami

AU - Asaumi, Noboru

AU - Huh, Nam ho

AU - Nakata, Yasunari

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