Neural invasion induces cachexia via astrocytic activation of neural route in pancreatic cancer

Authors

  • Akira Imoto,

    1. Pathology Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan
    2. Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka, Japan
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  • Shuichi Mitsunaga,

    1. Pathology Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan
    2. Division of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan
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  • Masatoshi Inagaki,

    1. Center for Suicide Prevention, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan
    2. Department of Neuropsychopharmacology, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan
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  • Kazuhiko Aoyagi,

    1. Genetics Division, National Cancer Center Research Institute, Chuo-Ku, Tokyo, Japan
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  • Hiroki Sasaki,

    1. Genetics Division, National Cancer Center Research Institute, Chuo-Ku, Tokyo, Japan
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  • Masafumi Ikeda,

    1. Division of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan
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  • Kohei Nakachi,

    1. Division of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan
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  • Kazuhide Higuchi,

    1. Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka, Japan
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  • Atsushi Ochiai

    Corresponding author
    1. Pathology Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan
    • Pathology Division, Research Center for Innovative Oncology, Kashiwanoha 6-5-1, Kashiwa, Chiba 277-8577, Japan
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    • Tel.: +81-471-34-6855; Fax: +81-471-34-6865


Abstract

Pancreatic cancer is characterized by a high frequency of cachexia, pain and neural invasion (N-inv). Neural damage is occurred by N-inv and modulates pain and muscle atrophy via the activation of astrocyte in the connected spine. The activated astrocyte by N-inv, thus, may affect cachexia in pancreatic cancer. Clinical studies in patients and autopsy cases with pancreatic cancer have revealed that N-inv is related to cachexia and astrocytic activation. We established a novel murine model of cancer cachexia using N-inv of human pancreatic cancer cells. Mice with N-inv showed a loss of body weight, skeletal muscle and fat mass without appetite loss, which are compatible with an animal model of cancer cachexia. Activation of astrocytes in the spinal cord connected with N-inv was observed in our model. Experimental cachexia was suppressed by disrupting neural routes or inhibiting the activation of astrocytes. These data provide the first evidence that N-inv induces cachexia via astrocytic activation of neural route in pancreatic cancer.

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