Prognostic significance of c‐Met expression in glioblastomas

Abstract

Objective Human Lyme arthritis caused by Borrelia burgdorferi is characterized by an inflammatory infiltrate that consists mainly of neutrophils and T cells. This study was undertaken to evaluate the role of the innate and acquired immune responses elicited by the neutrophil‐activating protein A (NapA) of B burgdorferi in patients with Lyme arthritis. Methods Serum anti‐NapA antibodies were measured in 27 patients with Lyme arthritis and 30 healthy control subjects. The cytokine profile of synovial fluid T cells specific for NapA was investigated in 5 patients with Lyme arthritis. The cytokine profile induced by NapA in neutrophils and monocytes was also investigated. Results Serum anti‐NapA antibodies were found in 48% of the patients with Lyme arthritis but were undetectable in the healthy controls. T cells from the synovial fluid of patients with Lyme arthritis produced interleukin‐17 (IL‐17) in response to NapA. Moreover, NapA was able to induce the expression of IL‐23 in neutrophils and monocytes, as well as the expression of IL‐6, IL‐1β, and transforming growth factor β (TGFβ) in monocytes, via Toll‐like receptor 2. Conclusion These findings indicate that NapA of B burgdorferi is able to drive the expression of IL‐6, IL‐1β, IL‐23, and TGFβ by cells of the innate immune system and to elicit a synovial fluid Th17 cell response that might play a crucial role in the pathogenesis of Lyme arthritis.

Emerging insights into the molecular and cellular basis of glioblastoma

“…The c-Met RTK is amplified in ;5% of glioblastomas, has been found to be overexpressed in 18 out of 62 (29%) glioblastoma samples with shorter median survival (Kong et al 2009), and is rarely mutated (The Cancer Genome Atlas Research Network 2008). Moreover, c-MET was found to be coactivated in glioblastoma cells with increased levels of EGFR/EGFRvIII Stommel et al 2007;Pillay et al 2009) and represents a critical dependency in MET-amplified cells (Beroukhim et al 2007).…”

The role of the PI3K/AKT/mTOR pathway in brain tumor metastasis

“…[97,98] In a recent study of 218 cases of human GBM, IGF-1R overexpression was reported as an independent prognostic factor associated with shorter survival time and a less favorable response to temozolomide. [99] C-MET expression levels correlate with tumor grade in CNS malignancies, [100] and its activation also mediates EMTpromoting signals in cancer cells via class I A PI3K. [101,102] In MB, c-MET signaling is deregulated, thus inducing tumor growth and an anaplastic histology.…”

The MET Oncogene Is a Functional Marker of a Glioblastoma Stem Cell Subtype

“…3A-C) indicated that not only EGFR alteration but also transcription was preferentially associated with classical neurospheres (2-sided t test, P < 0.0001). Vice versa, transcription of the MET gene, known to be expressed in a fraction (ffi30%) of unclassified human gliomas (19,20), was preferentially associated with mesenchymal/proneural neurospheres (2-sided t test, P < 0.01).…”