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 language | English |
|---|---|
| Pages (from-to) | 515-526 |
| Number of pages | 12 |
| Journal | International journal of molecular sciences |
| Volume | 14 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 1 2013 |
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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 journal › Article
}
TY - JOUR
T1 - IL-6 receptor is a possible target against growth of metastasized lung tumor cells in the brain
AU - Noda, Mami
AU - Yamakawa, Yukiko
AU - Matsunaga, Naoya
AU - Naoe, Satoko
AU - Jodoi, Taishi
AU - Yamafuji, Megumi
AU - Akimoto, Nozomi
AU - Teramoto, Norihiro
AU - Fujita, Kyota
AU - Ohdo, Shigehiro
AU - Iguchi, Haruo
PY - 2013/1/1
Y1 - 2013/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84872202767&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84872202767&partnerID=8YFLogxK
U2 - 10.3390/ijms14010515
DO - 10.3390/ijms14010515
M3 - Article
C2 - 23271367
AN - SCOPUS:84872202767
VL - 14
SP - 515
EP - 526
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 1
ER -