title: Activin signal promotes cancer progression and is involved in cachexia in a subset of pancreatic cancer.
abstract: We previously reported that activin produces a signal with a tumor suppressive role in pancreatic cancer (PC). Here, the association between plasma activin A and survival in patients with advanced PC was investigated. Contrary to our expectations, however, patients with high plasma activin A levels had a significantly shorter survival period than those with low levels (median survival, 314 days vs. 482 days, P = 0.034). The cellular growth of the MIA PaCa-2 cell line was greatly enhanced by activin A via non-SMAD pathways. The cellular growth and colony formation of an INHBA (beta subunit of inhibin)-overexpressed cell line were also enhanced. In a xenograft study, INHBA-overexpressed cells tended to result in a larger tumor volume, compared with a control. The bodyweights of mice inoculated with INHBA-overexpressed cells decreased dramatically, and these mice all died at an early stage, suggesting the occurrence of activin-induced cachexia. Our findings indicated that the activin signal can promote cancer progression in a subset of PC and might be involved in cachexia. The activin signal might be a novel target for the treatment of PC.
authors.affiliation: Department of Genome Biology, Kindai University Faculty of Medicine, Osaka, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Togashi
authors.affiliation: Department of Genome Biology, Kindai University Faculty of Medicine, Osaka, Japan; Department of Surgery, Kindai University Faculty of Medicine, Osaka, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kogita
authors.affiliation: Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Sakamoto
authors.affiliation: Department of Genome Biology, Kindai University Faculty of Medicine, Osaka, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Hayashi
authors.affiliation: Department of Genome Biology, Kindai University Faculty of Medicine, Osaka, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Terashima
authors.affiliation: Department of Genome Biology, Kindai University Faculty of Medicine, Osaka, Japan.
authors.forename: Marco A
authors.initials: MA
authors.lastname: de Velasco
authors.affiliation: Department of Genome Biology, Kindai University Faculty of Medicine, Osaka, Japan.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Sakai
authors.affiliation: Department of Genome Biology, Kindai University Faculty of Medicine, Osaka, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Fujita
authors.affiliation: Department of Genome Biology, Kindai University Faculty of Medicine, Osaka, Japan.
authors.forename: Shuta
authors.initials: S
authors.lastname: Tomida
authors.affiliation: Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kitano
authors.affiliation: Department of Surgery, Kindai University Faculty of Medicine, Osaka, Japan.
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Okuno
authors.affiliation: Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kudo
authors.affiliation: Department of Genome Biology, Kindai University Faculty of Medicine, Osaka, Japan. Electronic address: knishio@med.kindai.ac.jp.
authors.forename: Kazuto
authors.initials: K
authors.lastname: Nishio
mesh_terms: D028341:Activins / Q000235:genetics / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000097:blood*; D015153:Blotting, Western; D002100:Cachexia / Q000175:diagnosis / Q000209:etiology* / Q000401:mortality; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000150:complications / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; C422405:activin A; D028341:Activins
keywords: Activin signal; Cachexia; INHBA; INHBB; Pancreatic cancer