A Complementary Role for the Tetraspanins CD37 and Tssc6 in Cellular Immunity
JOURNAL OF IMMUNOLOGY
Authors: Gartlan, Kate H.; Belz, Gabrielle T.; Tarrant, Jacqueline M.; Minigo, Gabriela; Katsara, Maria; Sheng, Kuo-Ching; Sofi, Mariam; van Spriel, Annemiek B.; Apostolopoulos, Vasso; Plebanski, Magdalena; Robb, Lorraine; Wright, Mark D.
Abstract
The cooperative nature of tetraspanin-tetraspanin interactions in membrane organization suggests functional overlap is likely to be important in tetraspanin biology. Previous functional studies of the tetraspanins CD37 and Tssc6 in the immune system found that both CD37 and Tssc6 regulate T cell proliferative responses in vitro. CD37(-/-) mice also displayed a hyper-stimulatory dendritic cell phenotype and dysregulated humoral responses. In this study, we characterize "double knockout" mice (CD37(-/-) Tssc6(-/-)) generated to investigate functional overlap between these tetraspanins. Strong evidence for a cooperative role for these two proteins was identified in cellular immunity, where both in vitro T cell proliferative responses and dendritic cell stimulation capacity are significantly exaggerated in CD37(-/-) Tssc6(-/-) mice when compared with single knockout counterparts. Despite these exaggerated cellular responses in vitro, CD37(-/-) Tssc6(-/-) mice are not more susceptible to autoimmune induction. However, in vivo responses to pathogens appear poor in CD37(-/-) Tssc6(-/-) mice, which showed a reduced ability to produce influenza-specific T cells and displayed a rapid onset hyper-parasitemia when infected with Plasmodium yoelii. Therefore, in the absence of both CD37 and Tssc6, immune function is further altered when compared with CD37(-/-) or Tssc6(-/-) mice, demonstrating a complementary role for these two molecules in cellular immunity. The Journal of Immunology, 2010, 185: 3158-3166.
Prognostic significance of tetraspanin CD151 in newly diagnosed glioblastomas
JOURNAL OF SURGICAL ONCOLOGY
Authors: Lee, Dakeun; Suh, Yeon-Lim; Park, Tae-In; Do, In-Gu; Seol, Ho Jun; Nam, Do-Hyun; Kim, Sung Tae
Abstract
Background Tetraspanin CD151 is a positive effector of cancer invasion and metastasis. Methods We investigated the expression of CD151 by immunohistochemistry in 211 cases of grade I to IV gliomas. Additionally, we performed O6-methylguanin-DNA methyltransferase (MGMT) methylation analysis using real-time methylation-specific PCR in 36 patients with glioblastoma, and the prognostic significance of these biomarkers in glioblastomas was evaluated. Results Overexpression of CD151 was observed in a significant proportion (55.6%) of glioblastomas, while CD151 was rarely overexpressed in most of grade I to III glial tumors. CD151 overexpression was closely associated with MGMT methylation (P=0.014), and it was a prognostic factor for predicting worse overall survival (OS; P=0.002) and progression-free survival (PFS; P=0.043). We also found that combination of CD151 overexpression and MGMT methylation better stratified the patients' OS (P=0.001) and PFS (P=0.009). In multivariate analysis, CD151 overexpression was an independent prognostic factor for predicting OS over MGMT methylation (P=0.012). Conclusions CD151 seems to have a critical role for high-grade progression in astroglial tumors. Furthermore, CD151 is a good tissue marker that can be used easily in a daily practice for predicting worse prognosis in patients with glioblastoma. J. Surg. Oncol. 2013;107:646652. (c) 2012 Wiley Periodicals, Inc.