Roles of osteoclasts and bone-derived IGFs in the survival and growth of human breast cancer cells in human adult bone implanted into nonobese diabetic/severe combined immunodeficient mice

被引：11

作者：

Sangai, Takafumi ^{[1
,2
]}

Fujimoto, Hiroshi ^{[1
,2
]}

Miyamoto, Shin'ichi ^{[1
]}

Maeda, Hiroyuki ^{[1
]}

Nakamura, Michio ^{[1
]}

Ishii, Genichiro ^{[1
]}

Nagai, Kanji ^{[3
]}

Nagashima, Takeshi ^{[2
]}

Miyazaki, Masaru ^{[2
]}

Ochiai, Atsushi ^{[1
]}

机构：

[1] Natl Canc Ctr Hosp E, Res Ctr Innovat Oncol, Div Pathol, Kashiwa, Chiba 2778577, Japan

[2] Chiba Univ, Grad Sch Med, Dept Gen Surg, Chiba, Japan

[3] Natl Canc Ctr Hosp E, Div Thorac Oncol, Chiba, Japan

来源：

CLINICAL & EXPERIMENTAL METASTASIS | 2008年 / 25卷 / 04期

关键词：

antibody therapy; insulin-like growth factor; osteoclastogenesis inhibitory factor/osteoprotegerin; osteoclast; breast cancer; bone tumor;

D O I：

10.1007/s10585-008-9144-8

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Human breast cancer frequently metastasizes to bone, and effective therapies for patients with bone metastasis are required. However, the molecular mechanism for the bone metastasis of human breast cancer has not yet been fully elucidated. The present study aimed to evaluate the importance of active osteoclasts and bone-derived insulin-like growth factors (IGFs) for the survival and growth of breast cancer cells in bone. Human breast cancer cell line MCF-7 cells were injected into human adult bone (HAB) implanted into nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. The mice were then treated with recombinant human osteoclastogenesis inhibitory factor/osteoprotegerin (rhOCIF/OPG), a decoy receptor for receptor activator of NF-kappaB ligand (RANKL), or an anti-human IGF monoclonal antibody. Histomorphometric analyses revealed that both treatments significantly decreased the tumor area of MCF-7 cells in cross-sections of the implanted HAB to about 30% of the tumor area in control mice, but had no effect on the growth of subcutaneously injected MCF-7 cells. Consistent with the results for the tumor area in HAB, there were fewer osteoclasts in the implanted HAB in rhOCIF/OPG-treated mice than in vehicle-treated mice. However, treatment with the anti-human IGF monoclonal antibody had no effect on the number of osteoclasts in HAB. The results indicate that the active osteoclasts induced by RANKL and the IGFs released as a result of bone resorption by these osteoclasts play crucial roles in the survival and growth of human breast cancer cells in bone and suggest that neutralization of bone-derived IGFs will be effective in preventing the development of bone tumors in breast cancer patients.

引用

页码：401 / 410

页数：10

共 36 条

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