title: STAT3 activation is associated with cerebrospinal fluid interleukin-10 (IL-10) in primary central nervous system diffuse large B cell lymphoma.
abstract: Signal transducers and activators of transcription 3 (STAT3) are activated by various cytokines and oncogenes; however, the activity and pathogenesis of STAT3 in diffuse large B cell lymphoma of the central nervous system have not been thoroughly elucidated. We investigated the phosphorylation levels of STAT3 in 40 specimens of primary central nervous system diffuse large B-cell lymphoma (PCNS DLBCL) and analyzed the association between phsopho-STAT3 (pSTAT3) expression and cerebrospinal fluid (CSF) concentration of interleukin-10 (IL-10) or IL-6. Immunohistochemistry and Western blot analysis revealed that most of the specimens in PCNS DLBCL expressed pSTST3 protein, and a strong phosphorylation levels of STAT3 was statistically associated with high CSF IL-10 levels, but not with CSF IL-6 levels. Next, we demonstrated that recombinant IL-10 and CSF containing IL-10 induced the phosphorylation of STAT3 in PCNS DLBCL cells. Furthermore, molecular subtype classified by Hans' algorithm was correlated with pSTAT3 expression levels and CSF IL-10 levels. These results suggest that the STAT3 activity is correlated with CSF IL-10 level, which is a useful marker for STAT3 activity in PCNS DLBCLs.
authors.affiliation: Department of Neurosurgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Mizowaki
authors.affiliation: Department of Neurosurgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan. takasasa@med.kobe-u.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Sasayama
authors.affiliation: Department of Neurosurgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Department of Neurosurgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
authors.forename: Katsu
authors.initials: K
authors.lastname: Mizukawa
authors.affiliation: Department of Neurosurgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
authors.forename: Kumi
authors.initials: K
authors.lastname: Takata
authors.affiliation: Department of Neurosurgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nakamizo
authors.affiliation: Department of Neurosurgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
authors.forename: Hirotomo
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Department of Neurosurgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nagashima
authors.affiliation: Department of Neurosurgery, Nishi-Kobe Medical Center, Kobe, Japan.
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Nishihara
authors.affiliation: Department of Pathology for Regional Communication, Kobe University Hospital, Kobe, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Hirose
authors.affiliation: Department of Diagnostic Pathology, Kobe University Hospital, Kobe, Japan.
authors.forename: Tomoo
authors.initials: T
authors.lastname: Itoh
authors.affiliation: Department of Neurosurgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Kohmura
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D045744:Cell Line, Tumor; D016543:Central Nervous System Neoplasms / Q000145:classification / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D016403:Lymphoma, Large B-Cell, Diffuse / Q000145:classification / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009368:Neoplasm Transplantation; D010766:Phosphorylation; D011379:Prognosis; D011994:Recombinant Proteins / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*
chemical_list: D015415:Biomarkers; C508609:IL10 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D016753:Interleukin-10
keywords: Central nervous system; Cerebrospinal fluid; Diffuse large B-cell lymphoma; IL-10; Prognosis; STAT3