ABSTRACT
MUC5AC is a secretory mucin aberrantly expressed in various cancers. In lung cancer, MUC5AC is overexpressed in both primary and metastatic lesions; however, its functional role is not well understood. The present study was aimed at evaluating mechanistic role of MUC5AC on metastasis of lung cancer cells. Clinically, the overexpression of MUC5AC was observed in lung cancer patient tissues and was associated with poor survival. In addition, the overexpression of Muc5ac was also observed in genetically engineered mouse lung adenocarcinoma tissues (Kras(G12D); Trp53(R172H/+); AdCre) in comparison with normal lung tissues. Our functional studies showed that MUC5AC knockdown resulted in significantly decreased migration in two lung cancer cell lines (A549 and H1437) as compared with scramble cells. Expression of integrins (α5, ß1, ß3, ß4 and ß5) was decreased in MUC5AC knockdown cells. As both integrins and MUC5AC have a von Willebrand factor domain, we assessed for possible interaction of MUC5AC and integrins in lung cancer cells. MUC5AC strongly interacted only with integrin ß4. The co-localization of MUC5AC and integrin ß4 was observed both in A549 lung cancer cells as well as genetically engineered mouse adenocarcinoma tissues. Activated integrins recruit focal adhesion kinase (FAK) that mediates metastatic downstream signaling pathways. Phosphorylation of FAK (Y397) was decreased in MUC5AC knockdown cells. MUC5AC/integrin ß4/FAK-mediated lung cancer cell migration was confirmed through experiments utilizing a phosphorylation (Y397)-specific FAK inhibitor. In conclusion, overexpression of MUC5AC is a poor prognostic marker in lung cancer. MUC5AC interacts with integrin ß4 that mediates phosphorylation of FAK at Y397 leading to lung cancer cell migration.
Subject(s)
Focal Adhesion Protein-Tyrosine Kinases/physiology , Integrin beta4/physiology , Lung Neoplasms/pathology , Mucin 5AC/physiology , Signal Transduction/physiology , Animals , Cell Line, Tumor , Cell Movement , Cell Proliferation , Cisplatin/therapeutic use , Drug Resistance, Neoplasm , Humans , Integrin beta4/analysis , Male , Mice , Mucin 5AC/analysis , PhosphorylationABSTRACT
F-18-fluoro-deoxy-glucose positron emission tomography (PET) is highly sensitive and specific in the imaging of B-cell lymphomas. In contrast, its utility in the diagnostic evaluation of T-cell lymphomas is less defined. In this article, we present our finding utilizing PET in peripheral T-cell lymphomas (PTCL). A retrospective review of patients who underwent PET examinations at our institution produced 24 PET examinations among patients with PTCL. A lesion-based analysis was undertaken to evaluate the diagnostic accuracy of PET in PTCL. PET findings were compared with a standard of reference and sensitivity, specificity, positive and negative predictive values were calculated. PET had an overall sensitivity of 86% and specificity of 100%. PET had high sensitivity (95%) at nodal and non-cutaneous extra-nodal sites and poor sensitivity (13%) at cutaneous sites. The mean SUV of abnormal foci in anaplastic large cell lymphoma was 11 mg/ml (range: 3 - 40), and PTCL-unclassified was 8 mg/ml (range: 1 - 23).
Subject(s)
Fluorodeoxyglucose F18 , Lymphoma, T-Cell, Peripheral/diagnostic imaging , Positron-Emission Tomography , Radiopharmaceuticals , Adolescent , Adult , Aged , Aged, 80 and over , Disease-Free Survival , Female , Humans , Lymphoma, T-Cell, Cutaneous/diagnostic imaging , Lymphoma, T-Cell, Cutaneous/drug therapy , Lymphoma, T-Cell, Peripheral/drug therapy , Male , Middle Aged , Neoplasm Staging , Retrospective Studies , Sensitivity and Specificity , Survival Rate , Tomography, X-Ray Computed , Treatment OutcomeSubject(s)
Pulmonary Embolism/diagnosis , Spleen/diagnostic imaging , Splenic Infarction/diagnostic imaging , Tomography, Emission-Computed, Single-Photon , Diagnosis, Differential , Female , Humans , Middle Aged , Pulmonary Embolism/diagnostic imaging , Pulmonary Embolism/therapy , Radiopharmaceuticals , Technetium Tc 99m Sulfur Colloid , Tomography, X-Ray ComputedABSTRACT
Arthrobacter ilicis T(2) brings about a unique type of cometabolic structural rearrangement of longifolene, a sesquiterpene, resulting in the formation of an acid. Infrared, nuclear magnetic resonance, mass spectrometry, and decoupling studies indicate that the acid product has a sativenelike structure, which is confirmed by conversion of the acid to its methyl ester and hydrocarbon.
