Blockade of interleukin-6 receptor suppresses the proliferation of H460 lung cancer stem cells

  • Authors:
    • Hee Yi
    • Hee-Jung Cho
    • Soo-Min Cho
    • Kyul Jo
    • Jin-A Park
    • Na‑Hyun  Kim
    • Gordon L. Amidon
    • Jin-Suk Kim
    • Ho-Chul Shin
  • View Affiliations

  • Published online on: April 26, 2012     https://doi.org/10.3892/ijo.2012.1447
  • Pages: 310-316
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Abstract

IL-6/6R signaling is closely associated with tumor growth and poor prognosis. Although there is evidence that interleukin-6 receptor (IL-6R)-mediated signaling promotes the growth and malignancy of cancer, the role of IL-6R in cancer stem cells (CSCs) is poorly defined. This study investigated the role of IL-6R in the proliferation of CSCs. Sphere-forming cells were isolated from the H460 non-small cell lung cancer (NSCLC) cell line and identified as CSCs using confocal microscopy, RT-PCR and WST-1 assay. The H460 spheres demonstrated the typical characteristics of CSCs, including CD133 expression, upregulation of Nanog, self-renewal, and drug resistance to methotrexate (MTX) and fluorouracil (5-FU). The release of IL-6R and its ligand, IL-6, were quantitatively determined and compared between CSCs and non-CSCs. The concentration of soluble IL-6R (sIL-6R) was remarkably high in CSCs compared to that in non-CSCs. Furthermore, significant upregulation of the IL-6R gene was also observed in the CSCs. The growth of CSCs was significantly inhibited by transfection with IL-6R small-interfering RNA (siRNA), as well as with the IL-6R monoclonal antibody (mAb). In addition, blocking both IL-6R and IL-6 using siRNA or mAbs intensified the inhibition of CSC proliferation. These findings indicate that IL-6R is present in CSCs and has an important role in the proliferation of CSCs in the H460 lung cancer cell line. Therefore, we suggest that IL-6R is both a viable target for the development of CSC-directed lung cancer therapeutics and a potential CSC marker in NSCLC.

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July 2012
Volume 41 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Yi H, Cho H, Cho S, Jo K, Park J, Kim NH, Amidon GL, Kim J and Shin H: Blockade of interleukin-6 receptor suppresses the proliferation of H460 lung cancer stem cells. Int J Oncol 41: 310-316, 2012
APA
Yi, H., Cho, H., Cho, S., Jo, K., Park, J., Kim, N. ... Shin, H. (2012). Blockade of interleukin-6 receptor suppresses the proliferation of H460 lung cancer stem cells. International Journal of Oncology, 41, 310-316. https://doi.org/10.3892/ijo.2012.1447
MLA
Yi, H., Cho, H., Cho, S., Jo, K., Park, J., Kim, N., Amidon, G. L., Kim, J., Shin, H."Blockade of interleukin-6 receptor suppresses the proliferation of H460 lung cancer stem cells". International Journal of Oncology 41.1 (2012): 310-316.
Chicago
Yi, H., Cho, H., Cho, S., Jo, K., Park, J., Kim, N., Amidon, G. L., Kim, J., Shin, H."Blockade of interleukin-6 receptor suppresses the proliferation of H460 lung cancer stem cells". International Journal of Oncology 41, no. 1 (2012): 310-316. https://doi.org/10.3892/ijo.2012.1447