scholarly journals Immunohistochemical Distribution of Sphingosine Kinase 1 in Normal and Tumor Lung Tissue

2005 ◽  
Vol 53 (9) ◽  
pp. 1159-1166 ◽  
Author(s):  
Korey R. Johnson ◽  
Kristy Y. Johnson ◽  
Heather G. Crellin ◽  
Besim Ogretmen ◽  
Alice M. Boylan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Normal Tissue ◽  
Sphingosine Kinase ◽  
Normal Lung ◽  
Cancer Tissue ◽  
Apical Surface ◽  
Sphingosine Kinase 1 ◽  
Lung Cancer Tissue ◽  
Alveolar Cells ◽  
Sphingosine 1 Phosphate

Sphingosine kinase 1 (SK1) is a key enzyme critical to the sphingolipid metabolic pathway responsible for catalyzing the formation of the bioactive lipid sphingosine-1-phosphate. SK1-mediated production of sphingosine-1-phosphate has been shown to stimulate such biological processes as cell growth, differentiation, migration, angiogenesis, and inhibition of apoptosis. In this study, cell type–specific immunolocalization of SK1 was examined in the bronchus/terminal bronchiole of the lung. Strong immunopositive staining was evident at the apical surface of pseudostratified epithelial cells of the bronchus and underlying smooth muscle cells, submucosal serous glands, immature chondrocytes, type II alveolar cells, foamy macrophages, endothelial cells of blood vessels, and neural bundles. Immunohistochemical screening for SK1 expression was performed in 25 samples of normal/tumor patient matched non–small-cell lung cancer tissue and found that 25 of 25 tumor samples (carcinoid [5 samples], squamous [10 samples], and adenocarcinoma tumors [10 samples]), exhibited overwhelmingly positive immunostaining for SK1 as compared with patient-matched normal tissue. In addition, an approximately 2-fold elevation of SK1 mRNA expression was observed in lung cancer tissue versus normal tissue, as well as in several other solid tumors. Taken together, these findings define the localization of SK1 in lung and provide clues as to how SK1 may play a role in normal lung physiology and the pathophysiology of lung cancer.

Membrane proteomic analysis comparing squamous cell lung cancer tissue and tumour-adjacent normal tissue

2012 ◽  
Vol 319 (1) ◽  
pp. 118-124 ◽  
Author(s):  
Burong Li ◽  
Jiantong Chang ◽  
Yonglie Chu ◽  
Huafeng Kang ◽  
Jun Yang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Squamous Cell ◽  
Cell Lung Cancer ◽  
Proteomic Analysis ◽  
Normal Tissue ◽  
Squamous Cell Lung Cancer ◽  
Cancer Tissue ◽  
Adjacent Normal Tissue ◽  
Lung Cancer Tissue

scholarly journals Phospholipid dynamics in ex vivo lung cancer and normal lung explants

2021 ◽  
Author(s):  
Julia Lesko ◽  
Alexander Triebl ◽  
Elvira Stacher-Priehse ◽  
Nicole Fink-Neuböck ◽  
Jörg Lindenmann ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Lung Tissue ◽  
De Novo ◽  
Ex Vivo ◽  
Normal Lung Tissue ◽  
Normal Lung ◽  
Cancer Tissue ◽  
Glycerol Backbone ◽  
Lung Cancer Tissue

AbstractIn cancer cells, metabolic pathways are reprogrammed to promote cell proliferation and growth. While the rewiring of central biosynthetic pathways is being extensively studied, the dynamics of phospholipids in cancer cells are still poorly understood. In our study, we sought to evaluate de novo biosynthesis of glycerophospholipids (GPLs) in ex vivo lung cancer explants and corresponding normal lung tissue from six patients by utilizing a stable isotopic labeling approach. Incorporation of fully 13C-labeled glucose into the backbone of phosphatidylethanolamine (PE), phosphatidylcholine (PC), and phosphatidylinositol (PI) was analyzed by liquid chromatography/mass spectrometry. Lung cancer tissue showed significantly elevated isotopic enrichment within the glycerol backbone of PE, normalized to its incorporation into PI, compared to that in normal lung tissue; however, the size of the PE pool normalized to the size of the PI pool was smaller in tumor tissue. These findings indicate enhanced PE turnover in lung cancer tissue. Elevated biosynthesis of PE in lung cancer tissue was supported by enhanced expression of the PE biosynthesis genes ETNK2 and EPT1 and decreased expression of the PC and PI biosynthesis genes CHPT1 and CDS2, respectively, in different subtypes of lung cancer in publicly available datasets. Our study demonstrates that incorporation of glucose-derived carbons into the glycerol backbone of GPLs can be monitored to study phospholipid dynamics in tumor explants and shows that PE turnover is elevated in lung cancer tissue compared to normal lung tissue.

scholarly journals Relationship between the miRNA Profiles and Oncogene Mutations in Non-Smoker Lung Cancer. Relevance for Lung Cancer Personalized Screenings and Treatments

2021 ◽  
Vol 11 (3) ◽  
pp. 182
Author(s):  
Alberto Izzotti ◽  
Gabriela Coronel Vargas ◽  
Alessandra Pulliero ◽  
Simona Coco ◽  
Irene Vanni ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Practice ◽  
Mutation Analysis ◽  
P53 Mutation ◽  
Normal Lung ◽  
Cancer Tissue ◽  
Lung Cancer Tissue ◽  
Clinical Onset ◽  
Prediction Of Survival

Oncogene mutations may be drivers of the carcinogenesis process. MicroRNA (miRNA) alterations may be adaptive or pathogenic and can have consequences only when mutation in the controlled oncogenes occurs. The aim of this research was to analyze the interplay between miRNA expression and oncogene mutation. A total of 2549 miRNAs were analyzed in cancer tissue—in surrounding normal lung tissue collected from 64 non-smoking patients and in blood plasma. Mutations in 92 hotspots of 22 oncogenes were tested in the lung cancer tissue. MicroRNA alterations were related to the mutations occurring in cancer patients. Conversely, the frequency of mutation occurrence was variable and spanned from the k-ras and p53 mutation detected in 30% of patients to 20% of patients in which no mutation was detected. The prediction of survival at a 3-year follow up did not occur for mutation analysis but was, conversely, well evident for miRNA analysis highlighting a pattern of miRNA distinguishing between survivors and death in patients 3 years before this clinical onset. A signature of six lung cancer specific miRNAs occurring both in the lungs and blood was identified. The obtained results provide evidence that the analysis of both miRNA and oncogene mutations was more informative than the oncogene mutation analysis currently performed in clinical practice.

scholarly journals Mice Deficient in Sphingosine Kinase 1 Are Rendered Lymphopenic by FTY720

2004 ◽  
Vol 279 (50) ◽  
pp. 52487-52492 ◽  
Author(s):  
Maria L. Allende ◽  
Teiji Sasaki ◽  
Hiromichi Kawai ◽  
Ana Olivera ◽  
Yide Mi ◽  
...  
Keyword(s):  
Vascular Development ◽  
Sphingosine Kinase ◽  
Sphingosine Kinase 1 ◽  
Cellular Functions ◽  
Lymphocyte Trafficking ◽  
Signaling Molecule ◽  
Physiological Functions ◽  
Sphingosine 1 Phosphate ◽  
Sphingosine Kinases ◽  
S1p Receptor

Sphingosine-1-phosphate (S1P), a lipid signaling molecule that regulates many cellular functions, is synthesized from sphingosine and ATP by the action of sphingosine kinase. Two such kinases have been identified, SPHK1 and SPHK2. To begin to investigate the physiological functions of sphingosine kinase and S1P signaling, we generated mice deficient in SPHK1.Sphk1null mice were viable, fertile, and without any obvious abnormalities. Total SPHK activity in mostSphk1-/-tissues was substantially, but not completely, reduced indicating the presence of multiple sphingosine kinases. S1P levels in most tissues from theSphk1-/- mice were not markedly decreased. In serum, however, there was a significant decrease in the S1P level. Although S1P signaling regulates lymphocyte trafficking, lymphocyte distribution was unaffected in lymphoid organs ofSphk1-/- mice. The immunosuppressant FTY720 was phosphorylated and elicited lymphopenia in theSphk1null mice showing that SPHK1 is not required for the functional activation of this sphingosine analogue prodrug. The results with theseSphk1null mice reveal that some key physiologic processes that require S1P receptor signaling, such as vascular development and proper lymphocyte distribution, can occur in the absence of SPHK1.

scholarly journals P2.09-17 A Call to Action: Rapid Collection of Post-Mortem Lung Cancer Tissue in the Community to Enable Lung Cancer Research

2018 ◽  
Vol 13 (10) ◽  
pp. S767-S768
Author(s):  
T. Boyle ◽  
G. Quinn ◽  
M. Schabath ◽  
T. Munoz-Antonia ◽  
L. Duarte ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Research ◽  
Cancer Tissue ◽  
Post Mortem ◽  
Lung Cancer Tissue ◽  
Call To Action

Protein Z/protein Z-dependent protease inhibitor system in human non-small-cell lung cancer tissue

2012 ◽  
Vol 129 (4) ◽  
pp. e92-e96 ◽  
Author(s):  
Ewa Sierko ◽  
Marek Z. Wojtukiewicz ◽  
Lech Zimnoch ◽  
Krystyna Ostrowska-Cichocka ◽  
Piotr Tokajuk ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Protease Inhibitor ◽  
Small Cell Lung Cancer ◽  
Small Cell ◽  
Cancer Tissue ◽  
Lung Cancer Tissue ◽  
Small Cell Lung ◽  
Protein Z ◽  
Inhibitor System ◽  
Z Protein

Impaired Sphingosine-1-Phosphate Synthesis Induces Preeclampsia by Deactivating Trophoblastic YAP (Yes-Associated Protein) Through S1PR2 (Sphingosine-1-Phosphate Receptor-2)-Induced Actin Polymerizations

Hypertension ◽  
2021 ◽  
Author(s):  
Jiujiang Liao ◽  
Yangxi Zheng ◽  
Mingyu Hu ◽  
Ping Xu ◽  
Li Lin ◽  
...  
Keyword(s):  
Actin Polymerization ◽  
Sphingosine Kinase ◽  
Actin Dynamics ◽  
Extravillous Trophoblast ◽  
Trophoblast Invasion ◽  
Hippo Signaling ◽  
Dependent Manner ◽  
Sphingosine Kinase 1 ◽  
Sphingosine 1 Phosphate

Incomplete spiral artery remodeling, caused by impaired extravillous trophoblast invasion, is a fundamental pathogenic process associated with malplacentation and the development of preeclampsia. Nevertheless, the mechanisms controlling this regulation of trophoblast invasion are largely unknown. We report that sphingosine-1-phosphate synthesis and expression is abundant in healthy trophoblast, whereas in pregnancies complicated by preeclampsia the placentae are associated with reduced sphingosine-1-phosphate and lower SPHK1 (sphingosine kinase 1) expression and activity. In vivo inhibition of sphingosine kinase 1 activity during placentation in pregnant mice led to decreased placental sphingosine-1-phosphate production and defective placentation, resulting in a preeclampsia phenotype. Moreover, sphingosine-1-phosphate increased HTR8/SVneo (immortalized trophoblast cells) cell invasion in a Hippo-signaling–dependent transcriptional coactivator YAP (Yes-associated protein) dependent manner, which is activated by S1PR2 (sphingosine-1-phosphate receptor-2) and downstream RhoA/ROCK induced actin polymerization. Mutation-based YAP-5SA demonstrated that sphingosine-1-phosphate activation of YAP could be either dependent or independent of Hippo signaling. Together, these findings suggest a novel pathogenic pathway of preeclampsia via disrupted sphingosine-1-phosphate metabolism and signaling-induced, interrupted actin dynamics and YAP deactivation; this may lead to potential novel intervention targets for the prevention and management of preeclampsia.

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