Abstract
Melanoma is commonly associated with multi-organ metastasis, and bone is a frequent metastatic site for melanoma. However, the mechanism responsible for such melanoma-induced bone metastasis is still poorly understood. In the present study, the intracardiac inoculation of leukemia inhibitory factor (LIF)-producing human melanoma-derived cells (SEKI) developed osteolytic bone destruction in male BALB/cA-nu/nu nude mice. To elucidate the role of LIF in melanoma-induced osteolysis, cells were prepared in which the expression of LIF was reduced using a siRNA technique from the parent SEKI cells. Osteoclastogenesis was induced in the co-culture of LIF and/or SEKI cells with osteoblastic stromal cells in vitro, whereas the LIF-reduced SEKI cells did not induce osteoclastogenesis. The intracardiac inoculation of LIF-reduced SEKI cells resulted in a significant reduction in the incidence and number of bone metastasis in comparison to those in the mice inoculated with the parent SEKI cells. The expression of LIF was found in seven of nine human melanoma-derived cell lines, suggesting that LIF expression is a universal event in melanoma. These findings suggest that a potential role for LIF in the melanoma-induced bone metastasis possibly through the stimulation of osteoclastogenesis. LIF might therefore be a potentially effective drug target in the treatment of bone metastasis in melanoma.
| Original language | English |
|---|---|
| Pages (from-to) | 133-141 |
| Number of pages | 9 |
| Journal | Clinical and Experimental Metastasis |
| Volume | 26 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Feb 1 2009 |
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All Science Journal Classification (ASJC) codes
- Oncology
- Cancer Research
Cite this
A role for leukemia inhibitory factor in melanoma-induced bone metastasis. / Maruta, Shigeaki; Takiguchi, Soichi; Ueyama, Miho; Kataoka, Yasufumi; Oda, Yoshinao; Tsuneyoshi, Masazumi; Iguchi, Haruo.
In: Clinical and Experimental Metastasis, Vol. 26, No. 2, 01.02.2009, p. 133-141.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A role for leukemia inhibitory factor in melanoma-induced bone metastasis
AU - Maruta, Shigeaki
AU - Takiguchi, Soichi
AU - Ueyama, Miho
AU - Kataoka, Yasufumi
AU - Oda, Yoshinao
AU - Tsuneyoshi, Masazumi
AU - Iguchi, Haruo
PY - 2009/2/1
Y1 - 2009/2/1
N2 - Melanoma is commonly associated with multi-organ metastasis, and bone is a frequent metastatic site for melanoma. However, the mechanism responsible for such melanoma-induced bone metastasis is still poorly understood. In the present study, the intracardiac inoculation of leukemia inhibitory factor (LIF)-producing human melanoma-derived cells (SEKI) developed osteolytic bone destruction in male BALB/cA-nu/nu nude mice. To elucidate the role of LIF in melanoma-induced osteolysis, cells were prepared in which the expression of LIF was reduced using a siRNA technique from the parent SEKI cells. Osteoclastogenesis was induced in the co-culture of LIF and/or SEKI cells with osteoblastic stromal cells in vitro, whereas the LIF-reduced SEKI cells did not induce osteoclastogenesis. The intracardiac inoculation of LIF-reduced SEKI cells resulted in a significant reduction in the incidence and number of bone metastasis in comparison to those in the mice inoculated with the parent SEKI cells. The expression of LIF was found in seven of nine human melanoma-derived cell lines, suggesting that LIF expression is a universal event in melanoma. These findings suggest that a potential role for LIF in the melanoma-induced bone metastasis possibly through the stimulation of osteoclastogenesis. LIF might therefore be a potentially effective drug target in the treatment of bone metastasis in melanoma.
AB - Melanoma is commonly associated with multi-organ metastasis, and bone is a frequent metastatic site for melanoma. However, the mechanism responsible for such melanoma-induced bone metastasis is still poorly understood. In the present study, the intracardiac inoculation of leukemia inhibitory factor (LIF)-producing human melanoma-derived cells (SEKI) developed osteolytic bone destruction in male BALB/cA-nu/nu nude mice. To elucidate the role of LIF in melanoma-induced osteolysis, cells were prepared in which the expression of LIF was reduced using a siRNA technique from the parent SEKI cells. Osteoclastogenesis was induced in the co-culture of LIF and/or SEKI cells with osteoblastic stromal cells in vitro, whereas the LIF-reduced SEKI cells did not induce osteoclastogenesis. The intracardiac inoculation of LIF-reduced SEKI cells resulted in a significant reduction in the incidence and number of bone metastasis in comparison to those in the mice inoculated with the parent SEKI cells. The expression of LIF was found in seven of nine human melanoma-derived cell lines, suggesting that LIF expression is a universal event in melanoma. These findings suggest that a potential role for LIF in the melanoma-induced bone metastasis possibly through the stimulation of osteoclastogenesis. LIF might therefore be a potentially effective drug target in the treatment of bone metastasis in melanoma.
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UR - http://www.scopus.com/inward/citedby.url?scp=60449089627&partnerID=8YFLogxK
U2 - 10.1007/s10585-008-9223-x
DO - 10.1007/s10585-008-9223-x
M3 - Article
VL - 26
SP - 133
EP - 141
JO - Clinical and Experimental Metastasis
JF - Clinical and Experimental Metastasis
SN - 0262-0898
IS - 2
ER -