Macrophage/microglia-derived IL-1β induces glioblastoma growth via the STAT3/NF-κB pathway
Keitaro Kai, Yoshihiro Komohara, Shigeyuki Esumi, Yukio Fujiwara, Takahiro Yamamoto, Ken Uekawa, Kazutaka Ohta, Tatsuya Takezaki, Jun‐ichiro Kuroda, Naoki Shinojima, Tadashi Hamasaki, Akitake Mukasa
Abstract
Glioblastoma is a glioma characterized by highly malignant features. Numerous studies conducted on the relationship between glioblastoma and the microenvironment have indicated the significance of tumor-associated macrophages/microglia (TAMs) in glioblastoma progression. Since interleukin (IL)-1β secreted by TAMs has been suggested to promote glioblastoma growth, we attempted to elucidate the detailed mechanisms of IL-1β in glioblastoma growth in this study. A phospho-receptor tyrosine kinase array and RNA-sequencing studies indicated that IL-1β induced the activation of signal transducer and activator of transcription-3 and nuclear factor-kappa B signaling. Glioblastoma cells stimulated by IL-1β induced the production of IL-6 and CXCL8, which synergistically promoted glioblastoma growth via signal transducer and activator of transcription-3 and nuclear factor-kappa B signaling. By immunohistochemistry, IL-1β expression was seen on TAMs, especially in perinecrotic areas. These results suggest that IL-1β might be a useful target molecule for anti-glioblastoma therapy.