BackgroundGlioblastoma multiforme (GBM) is characterized by extensive local invasion, which is in contrast with extremely rare systemic metastasis of GBM. Molecular mechanisms inhibiting systemic metastasis of GBM would be a novel therapeutic candidate for GBM in the brain.MethodsPatient-derived GBM cells were primarily cultured from surgical samples of GBM patients and were inoculated into the brains of immune deficient BALB/c-nude or NOD-SCID IL2Rgammanull (NSG) mice. Human NK cells were isolated from peripheral blood mononucleated cells and expanded in vitro.ResultsPatient-derived GBM cells in the brains of NSG mice unexpectedly induced spontaneous lung metastasis although no metastasis was detected in BALB/c-nude mice. Based on the difference of the innate immunity between two mouse strains, NK cell activities of orthotopic GBM xenograft models based on BALB/c-nude mice were inhibited. NK cell inactivation induced spontaneous lung metastasis of GBM cells, which indicated that NK cells inhibit the systemic metastasis. In vitro cytotoxic activities of human NK cells against GBM cells indicated that cytotoxic activity of NK cells against GBM cells prevents systemic metastasis of GBM and that NK cells could be effective cell therapeutics against GBM. Accordingly, NK cells transplanted into orthotopic GBM xenograft models intravenously or intratumorally induced apoptosis of GBM cells in the brain and showed significant therapeutic effects.ConclusionsOur results suggest that innate NK immunity is responsible for rare systemic metastasis of GBM and that sufficient supplementation of NK cells could be a promising immunotherapeutic strategy for GBM in the brain.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-2034-y) contains supplementary material, which is available to authorized users.

We aimed to investigate the potential role and regulatory mechanism of long noncoding RNA tumor‐associated lncRNA expressed in chromosome 2 (TALNEC2) in breast cancer. The expression of TALNEC2 in breast cancer tissues and cells were investigated. MCF‐7 and MDA‐MB‐231 cells were transfected with small interfering RNA (siRNA) duplexes for targeting TALNEC2 (si‐TALNEC2), enhancer of zeste homolog 2 (EZH2; si‐EZH2) and p57KIP2 (si‐p57 KIP2), and their corresponding controls (si‐NC). The viability, colony forming ability, cell cycle, apoptosis, and autophagy of transfected cells were assessed. The expressions of p‐p38 mitogen‐activated protein kinase (MAPK) and nuclear factor κB (NF‐κB) pathway‐related proteins were investigated. The results showed that TALNEC2 was highly expressed in breast cancer tissues and cells. Knockdown of TALNEC2 significantly inhibited the malignant behaviors of MCF‐7 and MDA‐MB‐231 cells, including inhibiting cell viability and colony forming, arresting cell cycle at G0/G1 phase, inducing cell apoptosis, and promoting cell autophagy. EZH2 was a TALNEC2 binding protein, which was upregulated in breast cancer tissues and cells and could negatively regulate p57 KIP2. Effects of TALNEC2 knockdown on malignant behaviors of MCF‐7 cells were reversed by p57 KIP2 knockdown. The expressions of p‐p38, RelA, and RelB in MCF‐7 cells were decreased after knockdown of TALNEC2 or EZH2, which were reversed by knockdown of p57 KIP2 concurrently. In conclusion, TALNEC2 may play an oncogenic role in breast cancer by binding to EZH2 to target p57 KIP2. Activation of p‐p38 MAPK and NF‐κB pathways may be key mechanisms mediating the oncogenic role of TALNEC2 in breast cancer. TALNEC2 may serve as a promising target in the therapy of breast cancer.

Background: Zolbetuximab (IMAB362) is under investigation for treating advanced gastrointestinal tumors because it targets Claudin18.2 (CLDN18.2). CLDN18.2 is a promising molecule along with the presence of human epidermal growth factor receptor 2 in gastric cancer. This study evaluated cell block (CB) preparations of serous cavity effusions for the feasibility for CLDN18.2 protein expression and compared the results with those of biopsy or resection specimens. The association of CLDN18.2 expression in effusion samples and the clinicopathological features were also investigated.Methods: Cytological effusion specimens and matched surgical pathology biopsy or resection specimens of 43 gastric and gastroesophageal junctional cancer cases were stained for CLDN18.2 expression and quantified using immunohistochemistry based on the manufacturer's instructions. Results:Positive staining was detected in 34 (79.1%) tissue and 27 (62.8%) effusion CB samples in this study. When "positivity" was defined as moderate-to-strong staining in ≥40% viable tumor cells, CLDN18.2 expression was observed in 24 (55.8%) tissue and 22 (51.2%) effusion CB samples. A cutoff of 40% for CLDN18.2 positivity was used to demonstrate high concordance (83.7%) between cytology CB and tissue specimens. The results showed that CLDN18.2 expression in effusion specimens correlated with tumor size (p = .021) but not with sex, age at diagnosis, primary tumor location, staging, Lauren phenotype, cytomorphologic features, or Epstein-Barr virus infection. Cytological effusions with or without CLDN18.2 expression did not significantly affect overall survival.Conclusions: This study's results show that serous body cavity effusions may be suitable for CLDN18.2 biomarker testing; however, discordant cases should be interpreted cautiously.