IL-6 receptor is a possible target against growth of metastasized lung tumor cells in the brain

Mami Noda, Yukiko Yamakawa, Naoya Matsunaga, Satoko Naoe, Taishi Jodoi, Megumi Yamafuji, Nozomi Akimoto, Norihiro Teramoto, Kyota Fujita, Shigehiro Ohdo, Haruo Iguchi

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)515-526
Number of pages12
JournalInternational journal of molecular sciences
Volume14
Issue number1
DOIs
Publication statusPublished - Jan 1 2013

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Interleukin-6 Receptors
lungs
brain
Tumors
Brain
tumors
Cells
Lung
Growth
Astrocytes
Neoplasms
B-Lymphocytes
animal models
metastasis
Animal Models
Animals
Neoplasm Metastasis
Monoclonal antibodies
Conditioned Culture Medium
Nude Mice

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

IL-6 receptor is a possible target against growth of metastasized lung tumor cells in the brain. / Noda, Mami; Yamakawa, Yukiko; Matsunaga, Naoya; Naoe, Satoko; Jodoi, Taishi; Yamafuji, Megumi; Akimoto, Nozomi; Teramoto, Norihiro; Fujita, Kyota; Ohdo, Shigehiro; Iguchi, Haruo.

In: International journal of molecular sciences, Vol. 14, No. 1, 01.01.2013, p. 515-526.

Research output: Contribution to journalArticle

Noda, Mami ; Yamakawa, Yukiko ; Matsunaga, Naoya ; Naoe, Satoko ; Jodoi, Taishi ; Yamafuji, Megumi ; Akimoto, Nozomi ; Teramoto, Norihiro ; Fujita, Kyota ; Ohdo, Shigehiro ; Iguchi, Haruo. / IL-6 receptor is a possible target against growth of metastasized lung tumor cells in the brain. In: International journal of molecular sciences. 2013 ; Vol. 14, No. 1. pp. 515-526.
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