Pulmonary Cell News Volume 2.16 | Apr 25 2013

Control of Lung Vascular Permeability and Endotoxin-Induced Pulmonary Oedema by Changes in Extracellular Matrix Mechanics
Researchers showed that lung vascular permeability is controlled mechanically by changes in extracellular matrix structure. Their studies reveal that pulmonary vascular leakage can be increased by altering extracellular matrix compliance in vitro and by manipulating lysyl oxidase-mediated collagen crosslinking in vivo. Either decreasing or increasing extracellular matrix stiffness relative to normal levels disrupts junctional integrity and increases vascular leakage. [Nat Commun] Abstract

Bone Marrow Cells Expressing Clara Cell Secretory Protein Increase Epithelial Repair after Ablation of Pulmonary Clara Cells
To determine if transtracheal delivery of wild-type bone marrow Clara cell secretory protein (CCSP)⁺ cells is beneficial after ablation of lung CCSP⁺ cells, transgenic mice were treated with ganciclovir followed by transtracheal administration of CCSP⁺ or CCSP^– marrow cells. Compared with mice administered CCSP^– cells, mice treated with CCSP⁺ cells had more donor cells lining the airway epithelium, where they expressed epithelial markers including CCSP. [Mol Ther] Full Article

Cytochrome P450 2A13 Enhances the Sensitivity of Human Bronchial Epithelial Cells to Aflatoxin B1-Induced DNA Damage
The authors previously found that cytochrome P450 2A13 (CYP2A13) could increase the cytotoxic and apoptotic effects of aflatoxin B1 (AFB1) in immortalized human bronchial epithelial cells (BEAS-2B). However, the role of CYP2A13 in AFB1-induced DNA damage is unclear. Using BEAS-2B cells that stably express CYP2A13 (B-2A13), CYP1A2 (B-1A2), and CYP2A6 (B-2A6), they compared their effects in AFB1-induced DNA adducts, DNA damage, and cell cycle changes. [Toxicol Appl Pharmacol] Abstract

Proteomic and Ionomic Profiling Reveals Significant Alterations of Protein Expression and Calcium Homeostasis in Cystic Fibrosis Cells
Abnormal epithelial ion transport is the primary cause of persistent airway infections and chronic inflammation in cystic fibrosis patients. To gain further insight into the mechanisms of epithelial dysfunctions linked to cystic fibrosis transmembrane conductance regulator (CFTR) mutations, the authors performed and integrated proteomic and ionomic analysis of human bronchial epithelial IB3-1 cells and compared them with a CFTR-complemented isogenic cell line (C38). [Mol Biosyst] Abstract

The Effect of Gastric Juice on Interleukin-8 Production by Cystic Fibrosis Primary Bronchial Epithelial Cells
Scientists evaluated the effect of gastric juice (GJ) on interleukin-8 (IL-8) production by primary bronchial epithelial cells (PBEC), derived from a CF patient and a healthy subject. PBEC obtained from one donor and one receptor for lung transplantation were stimulated with GJ from patients “off” and “on” proton pump inhibitors. IL-8 levels were measured in the supernatant. [J Cyst Fibros] Abstract

LUNG CANCER

MicroRNA-449a Enhances Radiosensitivity in CL1-0 Lung Adenocarcinoma Cells
The authors aimed to identify a microRNA (miR) that can adjust radiosensitivity in lung adenocarcinoma cells. Two lung adenocarcinoma cell lines (CL1-0 and CL1-5) with different metastatic ability and radiosensitivity were used. They found that Overexpression of miR-449a in CL1-0 cells effectively increased irradiation-induced DNA damage and apoptosis, altered the cell cycle distribution and eventually led to sensitization of CL1-0 to irradiation. [PLoS One] Full Article

Stat3 Downstream Gene Product Chitinase 3-Like 1 Is a Potential Biomarker of Inflammation-Induced Lung Cancer in Multiple Mouse Lung Tumor Models and Humans
The authors conclude that secretory chitinase 3-like 1 (CHI3L1) plays an important role in inflammation-induced lung cancer formation and potentially serve as a biomarker for lung cancer prediction. Based on their previous publication and this work, this is the first animal study linking overexpression of CHI3L1 to various lung tumor mouse models. [PLoS One] Full Article

Regulation of Membrane-Type 1 Matrix Metalloproteinase Expression by Zonula Occludens-2 in Human Lung Cancer Cells
Tight junctions are composed of transmembrane proteins (occludin, claudins) linked to the actin cytoskeleton through cytoplasmic adaptor molecules including those of the zonula occludens family (ZO-1, -2, -3). Researchers evaluated the potential role of ZO-2 in the acquisition of invasive properties by tumor cells. In vivo, they showed a decrease of ZO-2 expression in bronchopulmonary cancers, with a preferential localization in the cytoplasm. [Clin Exp Metastasis] Abstract

In Vitro and In Vivo Effects of Geranylgeranyltransferase I Inhibitor P61A6 on Non-Small Cell Lung Cancer Cells
Three non-small cell lung cancer cell lines were used to test the ability of P61A6 to inhibit cell proliferation. Further characterization involved analyses of geranylgeranylation, membrane association and activation of RhoA, and anchorage-dependent and -independent growth, as well as cell cycle effects and examination of cell cycle regulators. [BMC Cancer] Abstract | Full Article

American Lung Association “State of the Air 2013” Report Finds Air Quality Improves Nationwide Despite More Spikes in Unhealthy Air Days
The American Lung Association’s “State of the Air 2013” report found significant progress in the reduction of year-round particle pollution (soot) across the nation, but many cities that ranked among the most polluted had more unhealthy days of high ozone (smog) and short-term particle pollution than in the 2012 report. Despite that uptick, “State of the Air 2013” shows that the air quality nationwide continues the long-term trend to much healthier air. [American Lung Association] Press Release

Extensive-Disease Small-Cell Lung Cancer (Newly Diagnosed)
Decision Resources found that, despite the numerous therapies in clinical development for extensive-disease small-cell lung cancer (SCLC), no emerging therapy is likely to replace etoposide (Bristol-Myers Squibb’s Etopophos/VePesid, generics)/carboplatin (generics) as the standard of care before 2022. Interviewed experts complain that treatment for SCLC has changed very little in decades, and, given the challenges of treating this aggressive disease and the current clinical pipeline, experts are pessimistic that the treatment landscape will improve in the near future. [Decision Resources, LLC] Press Release

National Institutes of Health (United States)

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Center for Biologics Evaluation and Research (United States)

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NEW ASCO/AACR Methods in Clinical Cancer Research
July 27-August 2, 2013
Vail, United States

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