Research article summary (published 29 Sep 2009):

Stat3 inhibition activates tumor macrophages and abrogates glioma growth in mice.

Full Abstract

As the main effector-cell population of the central nervous system, microglia (MG) are considered to play an important immunoregulatory function in a number of pathological conditions such as inflammation, trauma, degenerative disease, and brain tumors. Recent studies, however, have suggested that the anti-neoplastic function of MG may be suppressed in malignant brain tumors. Considering the proposed suppressive role of signal transducers and activators of transcription 3 (Stat3) in antitumor immunity, we evaluated the role of Stat3 inhibition on MG and macrophage (MP) activation and tumor growth in a murine glioma model. N9 MG cells were exposed to GL261 glioma conditioned medium (GL261-CM) and evaluated for Stat3 activity and cytokine expression. Furthermore, the role of Stat3 inhibition on MG and MP activation was studied both in vitro and in vivo. Finally, the effect of Stat3 inhibition on tumor growth was assessed in intracranial GL261 gliomas. GL261-CM increased Stat3 activity in N9 cells in vitro and resulted in overexpression of IL-10 and IL-6, and downregulation of IL1-beta, a pro-inflammatory cytokine. Inhibition of Stat3 by CPA-7 or siRNA reversed glioma-induced cytokine expression profile in N9 cells. Furthermore, inactivation of Stat3 in intracranial GL261 tumors by siRNA resulted in MG/MP activation and tumor growth inhibition. Glioma-induced MG and MP suppression may be mediated thorough Stat3. Inhibition of Stat3 function in tumor MG/MP may result in their activation and can potentially be used as an adjunct immunotherapy approach for gliomas.

Author information

Author/s: Zhang, Leying (L); Alizadeh, Darya (D); Van Handel, Michelle (M); Kortylewski, Marcin (M); Yu, Hua (H); Badie, Behnam (B);

Affiliation: Division of Neurosurgery, Beckman Research Institute, City of Hope Medical Center, Duarte, California, USA.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.

Journal: Glia (Glia), published in United States. (Language: eng)

Reference: 2009-Oct; vol 57 (issue 13) : pp 1458-67

Dates: Created 2009/08/31; Completed 2009/10/30;

PMID: 19306372, status: MEDLINE (last retrieval date: 10/30/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals Antineoplastic Agents - pharmacology Brain Neoplasms - pathology; physiopathology Cell Line, Tumor Cells, Cultured Chlorine Compounds - pharmacology Culture Media, Conditioned Glioma - pathology; physiopathology Interleukin-10 - metabolism

Interleukin-1beta - metabolism Interleukin-6 - metabolism Macrophages - physiology Mice Microglia - physiology Neoplasm Transplantation Platinum Compounds - pharmacology RNA, Small Interfering STAT3 Transcription Factor - antagonists & inhibitors; metabolism

Associated Chemicals: Antineoplastic Agents (0) ; Chlorine Compounds (0) ; Culture Media, Conditioned (0) ; Interleukin-1beta (0) ; Interleukin-6 (0) ; Platinum Compounds (0) ; RNA, Small Interfering (0) ; STAT3 Transcription Factor (0) ; Stat3 protein, mouse (0) ; trichloronitritodiammineplatinum(IV) (0) ; Interleukin-10 (130068-27-8)

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