| Budget Amount *help |
¥4,020,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥420,000)
Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
1. Effect of soluble vascular endothelial growth factor receptor-1(sVEGFR-1) on the prostate cancer growth in the bone
We first introduced mammalian expression vector encoding sVEGFR-1 gene into PC-3 human prostate cancer cells and established stable transfectant This transfectant was directly injected into the tibia of stymie nude mice, and we found that secreted sVEGFR-1 from PC-3 suppressed tumor growth and angiogenesis in the bone. Next, we introduced again same expression vector into rat bone marrow stromal cells (BMSCs). Successful expression and secretion was confirmed by ELISA method. By using these transient transfectant, further experiment was conducted. After pre-injection of PC-3 into the tibia of nude mice, sVEGFR-1-expressing BMSCs were injected to left ventricle or tumor lesion. However, in this model, the significant suppression of tumor growth was not observed.
2. Effect of osteoprotegerin (OPG) on osteolytic prostate cancer growth in the bone
We first introduced mammalia
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n impression vector encoding human OPG (hOPG) gene intoPG.-3 human prostate cancer cells and established stable transfectant This transfectant was directly injected into the tibia of nude mice, and we hind that secreted hOPG from PC-3 reduced the number of osteoclasts and suppressed osteolytic tumor growth in bone. Next, we introduced again same expression vector into BMSCs and performed same experiment as described above. As well as the previous results, the significant suppression of tumor growth was not observed.From these results, we supposed that hOPG might be effective by using as an agent of prevention for bone metastasis. We introduced same expression vector into mouse BMSCs and injected to the tibia of nude mice, and then PC-3 was injected to same region. This treatment significantly reduced the weight of tumor Fluorescent-labeled mouse BMSCs showed that BMSCs were differentiated into cartilage in normal tissue, whereas it existed together to the cancer cells in tumor legion.
From these results, BMSCs may be useful as a tool of searching for the factors involved in the suppression of prostate cancer bone metastasis, examination of its actual effects, and of elucidation of the mechanisms. Less
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