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

J Neurooncol. 2015 Sep;124(2):165-74. doi: 10.1007/s11060-015-1843-9. Epub 2015 Jun 17.

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.

Keywords: Central nervous system; Cerebrospinal fluid; Diffuse large B-cell lymphoma; IL-10; Prognosis; STAT3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Biomarkers / metabolism
  • Cell Line, Tumor
  • Central Nervous System Neoplasms / classification
  • Central Nervous System Neoplasms / diagnosis
  • Central Nervous System Neoplasms / metabolism*
  • Central Nervous System Neoplasms / pathology
  • Female
  • Humans
  • Interleukin-10 / metabolism*
  • Interleukin-6 / metabolism
  • Lymphoma, Large B-Cell, Diffuse / classification
  • Lymphoma, Large B-Cell, Diffuse / diagnosis
  • Lymphoma, Large B-Cell, Diffuse / metabolism*
  • Lymphoma, Large B-Cell, Diffuse / pathology
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Neoplasm Transplantation
  • Phosphorylation
  • Prognosis
  • Recombinant Proteins / metabolism
  • STAT3 Transcription Factor / metabolism*

Substances

  • Biomarkers
  • IL10 protein, human
  • IL6 protein, human
  • Interleukin-6
  • Recombinant Proteins
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Interleukin-10