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Int. J. Mol. Sci. 2013, 14(1), 515-526; doi:10.3390/ijms14010515
Article

IL-6 Receptor Is a Possible Target against Growth of Metastasized Lung Tumor Cells in the Brain

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Received: 30 November 2012; in revised form: 13 December 2012 / Accepted: 14 December 2012 / Published: 27 December 2012
(This article belongs to the Special Issue Brain Metastasis)
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Abstract: In the animal model of brain metastasis using human lung squamous cell carcinoma-derived cells (HARA-B) inoculated into the left ventricle of the heart of nude mice, metastasized tumor cells and brain resident cells interact with each other. Among them, tumor cells and astrocytes have been reported to stimulate each other, releasing soluble factors from both sides, subsequently promoting tumor growth significantly. Among the receptors for soluble factors released from astrocytes, only IL-6 receptor (IL-6R) on tumor cells was up-regulated during the activation with astrocytes. Application of monoclonal antibody against human IL-6R (tocilizumab) to the activated HARA-B cells, the growth of HARA-B cells stimulated by the conditioned medium of HARA-B/astrocytes was significantly inhibited. Injecting tocilizumab to animal models of brain metastasis starting at three weeks of inoculation of HARA-B cells, two times a week for three weeks, significantly inhibited the size of the metastasized tumor foci. The up-regulated expression of IL-6R on metastasized lung tumor cells was also observed in the tissue from postmortem patients. These results suggest that IL-6R on metastasized lung tumor cells would be a therapeutic target to inhibit the growth of the metastasized lung tumor cells in the brain.
Keywords: brain metastasis; tumor microenvironment; lung cancer; HARA-B cells; anti-IL-6R antibody; astrocytes brain metastasis; tumor microenvironment; lung cancer; HARA-B cells; anti-IL-6R antibody; astrocytes
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Noda, M.; Yamakawa, Y.; Matsunaga, N.; Naoe, S.; Jodoi, T.; Yamafuji, M.; Akimoto, N.; Teramoto, N.; Fujita, K.; Ohdo, S.; Iguchi, H. IL-6 Receptor Is a Possible Target against Growth of Metastasized Lung Tumor Cells in the Brain. Int. J. Mol. Sci. 2013, 14, 515-526.

AMA Style

Noda M, Yamakawa Y, Matsunaga N, Naoe S, Jodoi T, Yamafuji M, Akimoto N, Teramoto N, Fujita K, Ohdo S, Iguchi H. IL-6 Receptor Is a Possible Target against Growth of Metastasized Lung Tumor Cells in the Brain. International Journal of Molecular Sciences. 2013; 14(1):515-526.

Chicago/Turabian Style

Noda, Mami; Yamakawa, Yukiko; Matsunaga, Naoya; Naoe, Satoko; Jodoi, Taishi; Yamafuji, Megumi; Akimoto, Nozomi; Teramoto, Norihiro; Fujita, Kyota; Ohdo, Shigehiro; Iguchi, Haruo. 2013. "IL-6 Receptor Is a Possible Target against Growth of Metastasized Lung Tumor Cells in the Brain." Int. J. Mol. Sci. 14, no. 1: 515-526.


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