title: Neural invasion induces cachexia via astrocytic activation of neural route in pancreatic cancer.
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.
authors.affiliation: Pathology Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Imoto
authors.forename: Shuichi
authors.initials: S
authors.lastname: Mitsunaga
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Inagaki
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Aoyagi
authors.forename: Hiroki
authors.initials: H
authors.lastname: Sasaki
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ikeda
authors.forename: Kohei
authors.initials: K
authors.lastname: Nakachi
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Higuchi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ochiai
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000473:pathology*; D002100:Cachexia / Q000209:etiology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009420:Nervous System / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D010190:Pancreatic Neoplasms / Q000150:complications / Q000473:pathology*; D060888:Real-Time Polymerase Chain Reaction