A role for leukemia inhibitory factor in melanoma-induced bone metastasis

  • Shigeaki Maruta
  • Soichi Takiguchi
  • Miho Ueyama
  • Yasufumi Kataoka
  • Yoshinao Oda
  • Masazumi Tsuneyoshi
  • Haruo Iguchi
Research Paper


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.


Bone metastasis Leukemia inhibitory factor Melanoma Molecular target Osteoclastogenesis 



Leukemia inhibitory factor


Parathyroid hormone-related protein


Glyceraldehydes-3-phosphate dehydrogenase


Small interfering RNA


Tartrate-resistant acid phosphatase


3,3′-Diaminobenzidine tetrahydrochloride


Hematopoietic cells




Bone volume


Tissue volume


Eroded bone surface


Bone surface


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Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • Shigeaki Maruta
    • 1
  • Soichi Takiguchi
    • 1
  • Miho Ueyama
    • 2
  • Yasufumi Kataoka
    • 2
  • Yoshinao Oda
    • 3
  • Masazumi Tsuneyoshi
    • 3
  • Haruo Iguchi
    • 4
  1. 1.Institute for Clinical ResearchNational Kyushu Cancer CenterFukuokaJapan
  2. 2.Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical SciencesFukuoka UniversityFukuokaJapan
  3. 3.Department of Anatomical Pathology, Graduate school of Medical SciencesKyushu UniversityFukuokaJapan
  4. 4.Clinical Research InstituteShikoku Cancer CenterMatsuyamaJapan

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