scholarly journals EpCAM-Targeted 3WJ RNA Nanoparticle Harboring Delta-5-Desaturase siRNA Inhibited Lung Tumor Formation via DGLA Peroxidation

2020 ◽  
Vol 22 ◽  
pp. 222-235
Author(s):  
Lizhi Pang ◽  
Harshit Shah ◽  
Hongzhi Wang ◽  
Dan Shu ◽  
Steven Y. Qian ◽  
...  
Keyword(s):  
Lung Tumor ◽  
Tumor Formation ◽  
Delta 5 Desaturase

scholarly journals Leukotriene B4 receptor-2 contributes to KRAS-driven lung tumor formation by promoting interleukin-6-mediated inflammation

2021 ◽  
Author(s):  
Jae-Hyun Jang ◽  
Donghwan Park ◽  
Guen-soo Park ◽  
Dong-Wook Kwak ◽  
JaeIn Park ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Interleukin 6 ◽  
Double Mutant ◽  
Lung Tumor ◽  
Leukotriene B4 ◽  
Tumor Formation ◽  
Human Lung Cancer ◽  
Specific Expression ◽  
Tissue Samples ◽  
Attractive Therapeutic Target

AbstractAlthough lung cancer is the leading cause of cancer-related deaths worldwide and KRAS is the most frequently mutated oncogene in lung cancer cases, the mechanism by which KRAS mutation drives lung cancer has not been fully elucidated. Here, we report that the expression levels of leukotriene B4 receptor-2 (BLT2) and its ligand-producing enzymes (5-LOX, 12-LOX) were highly increased by mutant KRAS and that BLT2 or 5-/12-LOX blockade attenuated KRAS-driven lung cell proliferation and production of interleukin-6 (IL-6), a principal proinflammatory mediator of lung cancer development. Next, we explored the roles of BLT2 and 5-/12-LOX in transgenic mice with lung-specific expression of mutant KRAS (KrasG12D) and observed that BLT2 or 5-/12-LOX inhibition decreased IL-6 production and tumor formation. To further determine whether BLT2 is involved in KRAS-driven lung tumor formation, we established a KrasG12D/BLT2-KO double-mutant mouse model. In the double-mutant mice, we observed significantly suppressed IL-6 production and lung tumor formation. Additionally, we observed high BLT2 expression in tissue samples from patients with KrasG12D-expressing lung adenocarcinoma, supporting the contributory role of BLT2 in KRAS-driven human lung cancer. Collectively, our results suggest that BLT2 is a potential contributor to KRAS-driven lung cancer and identify an attractive therapeutic target for KRAS-driven lung cancer.

scholarly journals The Oncogenic Potential of a Mutant TP53 Gene Explored in Two Spontaneous Lung Cancer Mice Models

2020 ◽  
Author(s):  
Julian Ramelow ◽  
Christopher Brooks ◽  
Li GaO ◽  
Abeer A Almiman ◽  
Terence M Williams ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Mouse Models ◽  
Human Lung ◽  
Lung Tumor ◽  
Mutant Gene ◽  
Genetic Mutation ◽  
Tumor Formation ◽  
Human Lung Cancer ◽  
Oncogenic Potential ◽  
Age Related

Abstract BackgroundLung cancer is the number one cancer killer worldwide. A major impediment to progress in the lung cancer treatment field is the lack of realistic mouse models that replicate the complexity of human malignancy and immune contexture within the tumor microenvironment. Such models are urgently needed. Mutations of the tumor suppressor gene TP53 are among the most common alterations in human lung cancers.MethodsPreviously, we developed a line of lung cancer mouse model where mutant human TP53-273H is expressed in a lung specific manner in FVB/N background. To investigate whether the human TP53 mutant has a similar oncogenic potential when it is expressed in another strain of mouse, we crossed the FVB/N-SPC-TP53-273H mice to A/J strain and created A/J-SPC-TP53-273H transgenic mice. We then compared lung tumor formation between A/J-SPC-TP53-273H and FVB/N-SPC-TP53-273H.ResultsWe found the TP53-273H mutant gene has a similar oncogenic potential in lung tumor formation in both mice strains, although A/J strain mice have been found to be a highly susceptible strain in terms of carcinogen-induced lung cancer. Both transgenic lines survived more than 18 months and developed age related lung adenocarcinomas. With micro CT imaging, we found the FVB-SPC-TP53-273H mice survived more than 8 weeks after initial detection of lung cancer, providing a sufficient window for evaluating new anti-cancer agents.ConclusionsOncogenic potential of the most common genetic mutation, TP53-273H, in human lung cancer is unique when it is expressed in different strains of mice. Our mouse models are useful tools for testing novel immune check point inhibitors or other therapeutic strategies in treatment of lung cancer.

Abstract 313: K-ras- and EGFR-mediated lung tumor formation require epithelial NF-κB signaling to modulate the inflammatory microenvironment

2012 ◽  
Author(s):  
Jamie A. Ausborn ◽  
Taylor Sherrill ◽  
Rinat Zaynagetdinov ◽  
Vasiliy Polosukhin ◽  
Frank McMahon ◽  
...  
Keyword(s):  
Lung Tumor ◽  
Tumor Formation ◽  
Inflammatory Microenvironment

scholarly journals Expression of a Mutant p53 Results in an Age-Related Demographic Shift in Spontaneous Lung Tumor Formation in Transgenic Mice

PLoS ONE ◽  
2009 ◽  
Vol 4 (5) ◽  
pp. e5563 ◽  
Author(s):  
Wenrui Duan ◽  
Li Gao ◽  
Xin Wu ◽  
Erinn M. Hade ◽  
Jian-Xin Gao ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Lung Tumor ◽  
Tumor Formation ◽  
Mutant P53 ◽  
Demographic Shift ◽  
Age Related

scholarly journals Protein kinase Cα suppresses Kras-mediated lung tumor formation through activation of a p38 MAPK-TGFβ signaling axis

Oncogene ◽  
2013 ◽  
Vol 33 (16) ◽  
pp. 2134-2144 ◽  
Author(s):  
K S Hill ◽  
E Erdogan ◽  
A Khoor ◽  
M P Walsh ◽  
M Leitges ◽  
...  
Keyword(s):  
Protein Kinase ◽  
P38 Mapk ◽  
Lung Tumor ◽  
Tumor Formation ◽  
Tgfβ Signaling ◽  
Signaling Axis ◽  
Protein Kinase Cα

scholarly journals Overexpression of PRDX4 Modulates Tumor Microenvironment and Promotes Urethane-Induced Lung Tumorigenesis

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Jianbo Zheng ◽  
Xin Guo ◽  
Yuka Nakamura ◽  
Xiaolei Zhou ◽  
Reimon Yamaguchi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lung Cancer ◽  
Tumor Microenvironment ◽  
Tumor Cell ◽  
Lung Tumor ◽  
Interleukin 1 ◽  
Tumor Development ◽  
Tumor Model ◽  
Tumor Formation ◽  
Tumor Diameter

Peroxiredoxin 4 (PRDX4), initially reported as an antioxidant, is overexpressed in lung cancer and participates in its progression. However, its role in the urethane-induced lung tumor model is undetermined. The aim of this study was to investigate the effect of PRDX4 overexpression on carcinogen-induced lung tumor development. Human PRDX4 overexpression transgenic (Tg) mice (hPRDX4+/+) and non-Tg mice were intraperitoneally injected with urethane to induce lung tumor. After 6 months, tumor formation was compared between groups and possible mechanisms for the difference in tumor development were investigated. The serum and lung PRDX4 expressions were enhanced after urethane stimulation in Tg mice. Both the average number of tumors (≥0.5 mm) and tumor diameter per mouse in the Tg group were significantly larger than in non-Tg controls, while body weight was lower in the Tg group. Compared with non-Tg controls, tumor cell proliferation was enhanced, while tumor cell apoptosis was suppressed in Tg mice. Systemic oxidative stress and oxidative stress in lung tumors were inhibited by PRDX4 overexpression. The balance of prooxidant enzymes and antioxidant enzymes was also shifted to a decreased level in Tg tumor. In lung tumor tissue, the density of microvessel penetrated into tumor was higher in the Tg group; macrophage infiltration was enhanced in Tg tumors, while there was no difference in T lymphocyte infiltration; the expressions of cytokines, including interleukin-1 beta (IL-1β) and matrix metallopeptidase 9 (MMP9), were elevated in Tg tumors, which resulted from enhanced phosphorylation of nuclear factor-κB p65 (NF-κB p65) and c-Jun, respectively. In conclusion, PRDX4 overexpression modulated tumor microenvironment and promoted tumor development in the mouse urethane-induced lung cancer model.

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