IL-33/ST2 axis promotes glioblastoma cell invasion by accumulating tenascin-C.

Tenascin-C (TNC), a very large multimeric glycoprotein, is overexpressed in human glioblastomas, leading to a highly motile and invasive phenotype of glioma cells. However, the regulation of TNC expression in glioma has remained unclear until now. Our data suggest that interleukin-33 (IL-33) may promote the accumulation of TNC protein by autocrine or paracrine modes of action in glioma. In the present study, the expression levels of TNC, IL-33, and ST2 were measured in glioma tissue specimens, and the impact of altered IL-33 expression on TNC was investigated in vitro and in vivo. In contrast with control treatment, IL-33 treatment increased TNC expression, and knockdown of IL-33 attenuated TNC expression in glioma cells. Furthermore, IL-33 induced the activation of nuclear factor κB (NF-κB) and increased the expression of TNC in U251 cells. In addition, blockage of the IL-33-ST2-NFκB pathway resulted in downregulation of TNC production. IL-33 promoted glioma cell invasion by stimulating the secretion of TNC. Similarly, knockdown of TNC inhibited the invasiveness of glioma cells. These findings provide a novel perspective on the role of the IL-33/NF-κB/TNC signalling pathway in supporting cancer progression. Thus, targeting the IL-33/NF-κB/TNC signalling pathway may be a useful therapeutic approach in glioma.

IL­33 enhances glioma cell migration and invasion by upregulation of MMP2 and MMP9 via the ST2-NF-κB pathway.

As an important member of the interleukin (IL)-1 family, IL­33 plays a significant role in tumor progression. To explore this, we previously analyzed the association between IL­33 expression and the prognosis of patients with glioma. However, the function of the IL­33/ST2 axis in glioma remained unclear. In the present study, immunofluorescent staining results revealed that the expression levels of IL­33 and ST2 receptor in glioma tissues were higher than those in normal brain tissues. Invasion and migration assays demonstrated that IL­33 significantly increased glioma cell invasion and migration in vitro. Furthermore, knockdown of ST2 by siRNA attenuated the IL­33-induced increase in invasion and migration. In addition, ELISA results revealed that IL­33 upregulated the expression of matrix metalloproteinase (MMP)2 and MMP9. Western blot analysis results indicated that IL­33 stimulation increased the phosphorylation of nuclear factor-κB (NF-κB) in a time- and dose-dependent manner. Moreover, silencing of the NF-κB pathway by BAY 11­7082 resulted in the inhibition of IL­33-induced invasion and migration, as well as the downregulation of MMP2 and MMP9 production. These findings indicate that IL­33 may be involved in the process of glioma cell invasion and migration by upregulating MMP2 and MMP9 via the ST2-NF-κB signaling pathway. Thus, IL­33 may be a novel therapeutic target for glioma.

Anatomical study of endoscope-assisted far lateral keyhole approach to the ventral craniocervical region with neuronavigational guidance.

BACKGROUND: Image-guided neurosurgery, endoscopic-assisted neurosurgery and the keyhole approach are three important parts of minimally invasive neurosurgery and have played a significant role in treating skull base lesions. This study aimed to investigate the potential usefulness of coupling of the endoscope with the far lateral keyhole approach and image guidance at the ventral craniocervical junction in a cadaver model. METHODS: We simulated far lateral keyhole approach bilaterally in five cadaveric head specimens (10 cranial hemispheres). Computed tomography-based image guidance was used for intraoperative navigation and for quantitative measurements. Skull base structures were observed using both an operating microscope and a rigid endoscope. The jugular tubercle and one-third of the occipital condyle were then drilled, and all specimens were observed under the microscope again. We measured and compared the exposure of the petroclivus area provided by the endoscope and by the operating microscope. Statistical analysis was performed by analysis of variance followed by the Student-Newman-Keuls test. RESULTS: With endoscope assistance and image guidance, it was possible to observe the deep ventral craniocervical junction structures through three nerve gaps (among facial-acoustical nerves and the lower cranial nerves) and structures normally obstructed by the jugular tubercle and occipital condyle in the far lateral keyhole approach. The surgical area exposed in the petroclival region was significantly improved using the 0° endoscope (1147.80 mm(2)) compared with the operating microscope ((756.28 ± 50.73) mm(2)). The far lateral retrocondylar keyhole approach, using both 0° and 30° endoscopes, provided an exposure area ((1147.80 ± 159.57) mm(2) and (1409.94 ± 155.18) mm(2), respectively) greater than that of the far lateral transcondylar transtubercular keyhole approach ((1066.26 ± 165.06) mm(2)) (P < 0.05). CONCLUSIONS: With the aid of the endoscope and image guidance, it is possible to approach the ventral craniocervical junction with the far lateral keyhole approach. The use of an angled-lens endoscope can significantly improve the exposure of the petroclival region without drilling the jugular tubercle and occipital condyle.