Interferon γ mediated induction of apoptosis in primary human neuroendocrine tumor cells

2001 ◽  
Vol 120 (5) ◽  
pp. A509-A509
Author(s):  
A DROST ◽  
J KEHRBERGER ◽  
U PLOECKINGER ◽  
B WIEDENMANN ◽  
S ROSEWICZ ◽  
...  
2000 ◽  
Vol 118 (4) ◽  
pp. A531
Author(s):  
Katharina M. Detjen ◽  
Jenny Kehrberger ◽  
Anja Rabien ◽  
Martina Welzel ◽  
Bertram Wiedenmann ◽  
...  

2001 ◽  
Vol 120 (5) ◽  
pp. A509
Author(s):  
Adriana C. Drost ◽  
Jenny P. Kehrberger ◽  
Ursula Ploeckinger ◽  
Bertram Wiedenmann ◽  
Stefen Rosewicz ◽  
...  

Author(s):  
Annette Paschen ◽  
Ignacio Melero ◽  
Antoni Ribas

Resistance to immunotherapy is due in some instances to the acquired stealth mechanisms of tumor cells that lose expression of MHC class I antigen–presenting molecules or downregulate their class I antigen–presentation pathways. Most dramatically, biallelic β2-microglobulin (B2M) loss leads to complete loss of MHC class I expression and to invisibility to CD8+ T cells. MHC class I expression and antigen presentation are potently upregulated by interferon-γ (IFNγ) in a manner that depends on IFNγ receptor (IFNGR) signaling via JAK1 and JAK2. Mutations in these molecules lead to IFNγ unresponsiveness and mediate loss of recognition and killing by cytotoxic T lymphocytes. Loss of MHC class I augments sensitivity of tumor cells to be killed by natural killer (NK) lymphocytes, and this mechanism could be exploited to revert resistance, for instance, with interleukin-2 (IL-2)-based agents. Moreover, in some experimental models, potent local type I interferon responses, such as those following intratumoral injection of Toll-like receptor 9 (TLR9) or TLR3 agonists, revert resistance due to mutations of JAKs. Expected final online publication date for the Annual Review of Cancer Biology, Volume 6 is April 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.


2003 ◽  
Vol 36 (9) ◽  
pp. 1127-1129 ◽  
Author(s):  
Hideaki Nagami ◽  
Keiichi Yamamoto ◽  
Hideaki Ichihara ◽  
Yoko Matsumoto ◽  
Ryuichi Ueoka

2008 ◽  
Vol 199 (2) ◽  
pp. 177-189 ◽  
Author(s):  
Marta Labeur ◽  
Damian Refojo ◽  
Barbara Wölfel ◽  
Johanna Stalla ◽  
Vivian Vargas ◽  
...  

Interferon-γ (IFNG) is a cytokine that exerts potent antiproliferative and tumoricidal effects in a variety of cancers. Moreover, IFNG modulates normal pituitary hormone secretion, and was shown to inhibit the expression of the ACTH precursor POMC in murine ACTH-secreting AtT-2010/21/2008 tumor cells. We have studied the functional role of IFNG on pituitary tumor cells, focusing on the involvement of IFNG in the molecular events leading to the control of POMC transcriptional repression. Herein, it is shown that IFNG inhibits AtT-20 tumor cell proliferation without inducing apoptosis. Unexpectedly, an activated janus kinases–signal transducer and activator of transcription (JAK–STAT1) cascade is required for IFNG inhibitory action on POMC promoter activity. Factor-kappa B (NF-κB) is necessary for the inhibitory action of IFNG on Pomc transcription, since loss of NF-κB activity with IκB super-repressor abolishes this effect. In addition, 1 and 2 IFNG receptor immunoreactivity was detected in human corticotropinoma cells. Interestingly, IFNG inhibits ACTH production from these cells in primary cell culture, without affecting basal ACTH biosynthesis in normal non-tumoral pituitary cells. In conclusion, our data show for the first time that POMC transcription can be negatively regulated by a JAK–STAT1 and NF-κB-dependent pathway.


2019 ◽  
Vol 10 (2-3) ◽  
pp. 107-119
Author(s):  
Aura D. Herrera-Martínez ◽  
Richard A. Feelders ◽  
Wouter W. de Herder ◽  
Justo P. Castaño ◽  
María Ángeles Gálvez Moreno ◽  
...  

2020 ◽  
Vol 19 (10) ◽  
pp. 1619-1631
Author(s):  
Elez D. Vainer ◽  
Juliane Kania-Almog ◽  
Ghadeer Zatara ◽  
Yishai Levin ◽  
Gilad W. Vainer

Using a simple, environment friendly proteome extraction (TOP), we were able to optimize the analysis of clinical samples. Using our TOP method we analyzed a clinical cohort of microsatellite stable (MSS) and unstable (MSI-H) colorectal carcinoma (CRC). We identified a tumor cell specific, STAT1-centered, immune signature expressed by the MSI-H tumor cells. We then showed that long, but not short, exposure to Interferon-γ induces a similar signature in vitro. We identified 10 different temporal protein expression patterns, classifying the Interferon-γ protein temporal regulation in CRC. Our data sheds light on the changes that tumor cells undergo under long-term immunological pressure in vivo, the importance of STAT proteins in specific biological scenarios. The data generated could help find novel clinical biomarkers and therapeutic approaches.


2020 ◽  
Vol 11 ◽  
Author(s):  
Xiaoyu Wang ◽  
Yuanjian Fang ◽  
Yunxiang Zhou ◽  
Xiaoming Guo ◽  
Ke Xu ◽  
...  

BackgroundNonfunctioning pituitary neuroendocrine tumor (NF-PitNET) is difficult to resect. Except for surgery, there is no effective treatment for NF-PitNET. MicroRNA-134 (miR-134) has been reported to inhibit proliferation and invasion ability of tumor cells. Herein, the mechanism underlying the effect of miR-134 on alleviating NF-PitNET tumor cells growth is explored.MethodsMouse pituitary αT3-1 cells were transfected with miR-134 mimics and inhibitor, followed by treatment with stromal cell-derived factor-1α (SDF-1α) in vitro. MiR-134 expression level: we used quantitative real-time PCR (qRT-PCR) to detect the expression of miR-134. Cell behavior level: cell viability and invasion ability were assessed using a cell counting kit-8 (CCK8) assay and Transwell invasion assay respectively. Cytomolecular level: tumor cell proliferation was evaluated by Ki-67 staining; propidium iodide (PI) staining analyzed the effect of miR-134 on cell cycle arrest; western blot analysis and immunofluorescence staining evaluated tumor migration and invasive ability. Additionally, we collected 27 NF-PitNET tumor specimens and related clinical data. The specimens were subjected to qRT-PCR to obtain the relative miR-134 expression level of each specimen; linear regression analysis was used to analyze the miR-134 expression level in tumor specimens and the age of the NF-PitNET population, gender, tumor invasion, prognosis, and other indicators.ResultsIn vitro experiment, miR-134 was observed to significantly inhibit αT3-1 cells proliferation characterized by inhibited cell viability and expressions of vascular endothelial growth factor A (VEGFA) and cell cycle transition from G1 to S phase (P < 0.01). VEGFA was verified as a target of miR-134. Additionally, miR-134-induced inhibition of αT3-1 cell proliferation and invasion was attenuated by SDF-1α and VEGFA overexpression (P < 0.01). In primary NF-PitNET tumor analysis, miR-134 expression level was negatively correlated with tumor invasion (P = 0.003).ConclusionThe regulation of the SDF-1α/miR-134/VEGFA axis represents a novel mechanism in the pathogenesis of NF-PitNETs and may serve as a potential therapeutic target for the treatment of NF-PitNETs.


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