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

Akira Imoto, Shuichi Mitsunaga, Masatoshi Inagaki, Kazuhiko Aoyagi, Hiroki Sasaki, Masafumi Ikeda, Kohei Nakachi, Kazuhide Higuchi, Atsushi Ochiai

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17 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2795-2807
Number of pages13
JournalInternational Journal of Cancer
Volume131
Issue number12
DOIs
Publication statusPublished - Dec 15 2012

Keywords

  • animal model
  • cachexia
  • glial activation
  • neural invasion
  • pancreatic cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Imoto, A., Mitsunaga, S., Inagaki, M., Aoyagi, K., Sasaki, H., Ikeda, M., Nakachi, K., Higuchi, K., & Ochiai, A. (2012). Neural invasion induces cachexia via astrocytic activation of neural route in pancreatic cancer. International Journal of Cancer, 131(12), 2795-2807. https://doi.org/10.1002/ijc.27594