Tumor Necrosis Factor-α Produced by Osteoclasts Might Induce Intractable Pain in a Rat Spinal Metastasis Model of Breast Cancer

破骨细胞产生的肿瘤坏死因子-α 可能会在乳腺癌大鼠脊柱转移模型中诱发难治性疼痛

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作者:Ai Mazaki, Sumihisa Orita, Kazuhide Inage, Miyako Suzuki, Kohki Abe, Yasuhiro Shiga, Masahiro Inoue, Masaki Norimoto, Tomotaka Umimura, Seiji Ohtori, Kazuyo Yamauchi

Conclusions

The number of osteoclasts is higher in the metastasis model. While TNF in the osteoclasts increased in the spinal metastasis model, IL-6 did not. This probably means that breast cancer affects TNF production in osteoclasts. This increase of TNF-α may lead to pain from spinal metastasis.

Methods

We made a rat spinal metastasis model of breast cancer (metastasis group) and models with a hole in the vertebrae (puncture group) and resected the vertebrae. Tartrate-resistant acid phosphatase (TRAP) staining was performed to reconfirm that osteoclasts increase in vertebrae with spinal metastasis. We then evaluated TNF-α and IL-6 expression using immunohistochemistry and real-time polymerase chain reaction (PCR).

Results

The results of TRAP staining showed that osteoclasts increase in metastatic vertebrae. The osteoclasts in the puncture models were TNF-α negative but were TNF-α positive in the metastasis model. The osteoclasts in the puncture models and metastasis model were both IL-6 positive. According to the real-time PCR results, TNF-α in vertebrae increased in the metastasis model, but IL-6 did not increase in the metastasis model compared with in the puncture model. Conclusions: The number of osteoclasts is higher in the metastasis model. While TNF in the osteoclasts increased in the spinal metastasis model, IL-6 did not. This probably means that breast cancer affects TNF production in osteoclasts. This increase of TNF-α may lead to pain from spinal metastasis.

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