Journal of Neuro-Oncology

, Volume 124, Issue 2, pp 165–174 | Cite as

STAT3 activation is associated with cerebrospinal fluid interleukin-10 (IL-10) in primary central nervous system diffuse large B cell lymphoma

  • Takashi Mizowaki
  • Takashi Sasayama
  • Kazuhiro Tanaka
  • Katsu Mizukawa
  • Kumi Takata
  • Satoshi Nakamizo
  • Hirotomo Tanaka
  • Hiroaki Nagashima
  • Masamitsu Nishihara
  • Takanori Hirose
  • Tomoo Itoh
  • Eiji Kohmura
Laboratory Investigation


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.


Central nervous system Diffuse large B-cell lymphoma Cerebrospinal fluid STAT3 IL-10 Prognosis 


Conflict of interest



This study was supported in part by a Grant-in-Aid for Scientific Research to Eiji Kohmura (25293309), Takashi Sasayama (25462258), and Kazuhiro Tanaka (24791501) from the Japanese Ministry of Education, Culture, Sports, Science and Technology.

Supplementary material

11060_2015_1843_MOESM1_ESM.tif (843 kb)
Supplementary material 1 (TIFF 842 kb) Supplementary Fig. 1 Histological examinations of HKBML tumors implanted into nude mice. HKBML PCNSL cells (5 x 106/200 μl) were injected s.c. into the right flank of nude mice (BALB-c nu/nu). After 2 weeks, the tumor was removed, fixed, and analyzed by immunohistochemistry. The HKBML tumor was identified as a non-GCB type tumor. (Original magnification: × 400)


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Takashi Mizowaki
    • 1
  • Takashi Sasayama
    • 1
  • Kazuhiro Tanaka
    • 1
  • Katsu Mizukawa
    • 1
  • Kumi Takata
    • 1
  • Satoshi Nakamizo
    • 1
  • Hirotomo Tanaka
    • 1
  • Hiroaki Nagashima
    • 1
  • Masamitsu Nishihara
    • 2
  • Takanori Hirose
    • 3
  • Tomoo Itoh
    • 4
  • Eiji Kohmura
    • 1
  1. 1.Department of NeurosurgeryKobe University Graduate School of MedicineChuo-kuJapan
  2. 2.Department of NeurosurgeryNishi-Kobe Medical CenterKobeJapan
  3. 3.Department of Pathology for Regional CommunicationKobe University HospitalKobeJapan
  4. 4.Department of Diagnostic PathologyKobe University HospitalKobeJapan

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