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

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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.

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Conflict of interest

None.

Funding

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.

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Authors and Affiliations

  1. Department of Neurosurgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan

    Takashi Mizowaki, Takashi Sasayama, Kazuhiro Tanaka, Katsu Mizukawa, Kumi Takata, Satoshi Nakamizo, Hirotomo Tanaka, Hiroaki Nagashima & Eiji Kohmura

  2. Department of Neurosurgery, Nishi-Kobe Medical Center, Kobe, Japan

    Masamitsu Nishihara

  3. Department of Pathology for Regional Communication, Kobe University Hospital, Kobe, Japan

    Takanori Hirose

  4. Department of Diagnostic Pathology, Kobe University Hospital, Kobe, Japan

    Tomoo Itoh

Authors
  1. Takashi Mizowaki
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  2. Takashi Sasayama
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  3. Kazuhiro Tanaka
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  4. Katsu Mizukawa
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  5. Kumi Takata
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  6. Satoshi Nakamizo
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  7. Hirotomo Tanaka
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  8. Hiroaki Nagashima
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  9. Masamitsu Nishihara
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  10. Takanori Hirose
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  11. Tomoo Itoh
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  12. Eiji Kohmura
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Corresponding author

Correspondence to Takashi Sasayama.

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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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Mizowaki, T., Sasayama, T., Tanaka, K. et al. STAT3 activation is associated with cerebrospinal fluid interleukin-10 (IL-10) in primary central nervous system diffuse large B cell lymphoma. J Neurooncol 124, 165–174 (2015). https://doi.org/10.1007/s11060-015-1843-9

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  • DOI: https://doi.org/10.1007/s11060-015-1843-9

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