Rearranged during transfection (RET) fusions have been newly identified in approximately 1% of patients with primary lung tumors. However, patient-derived lung cancer cell lines harboring RET fusions have not yet been established or identified, and therefore, the effectiveness of an RET inhibitor on lung tumors with endogenous RET fusion has not yet been studied. In this study, we report identification of CCDC6-RET fusion in the human lung adenocarcinoma cell line LC-2/ad. LC-2/ad showed distinctive sensitivity to the RET inhibitor, vandetanib, among 39 non-small lung cancer cell lines. The xenograft tumor of LC-2/ad showed cribriform acinar structures, a morphologic feature of primary RET fusion-positive lung adenocarcinomas. LC-2/ad cells could provide useful resources to analyze molecular functions of RET-fusion protein and its response to RET inhibitors.
Early pulmonary resection is indicated in patients with hemoptysis of multiple branches from the cavity and chest wall, such as in fungal infections. When a bronchial branch is the only bleeding focus, superselective embolotherapy should be considered prior to surgery even if the localized focus of the bronchial branch shows minor vascularity on the angiography.
Decreased cell-substratum adhesion is crucially involved in metastasis. Previous studies demonstrated that lung cancer with floating cell clusters in histology is more likely to develop metastasis. In the present study, we investigated whether cancer cells in long-term, three-dimensional low attachment cultures acquire high metastatic potential; these cells were then used to examine the mechanisms underlying metastasis. Two KRAS-mutated adenocarcinoma cell lines (A549 and H441) were cultured and selected on ultra-low attachment culture dishes, and the resulting cells were defined as FL (for floating) sublines. Cancer cells were inoculated into NOD/SCID mice via an intracardiac injection, and metastasis was evaluated using luciferase-based imaging and histopathology. In vitro cell growth (in attachment or suspension cultures), migration, and invasion were assayed. A whole genomic analysis was performed to identify key molecular alterations in FL sublines. Upon detachment on low-binding dishes, parental cells initially formed rounded spheroids with limited growth activity. However, over time in cultures, cells gradually formed smaller spheroids that grew slowly, and, after 3–4 months, we obtained FL sublines that regained prominent growth potential in suspension cultures. On ordinary dishes, FL cells reattached and exhibited a more spindle-shaped morphology than parental cells. No marked differences were observed in cell growth with attachment, migration, or invasion between FL sublines and parental cell lines; however, FL cells exhibited markedly increased growth potential under suspended conditions in vitro and stronger metastatic abilities in vivo. A genomic analysis identified epithelial-mesenchymal transition (EMT) and c-Myc amplification in A549-FL and H441-FL cells, respectively, as candidate mechanisms for metastasis. The growth potential of FL cells was markedly inhibited by lentiviral ZEB1 knockdown in A549-FL cells and by the inhibition of c-Myc through lentiviral knockdown or the pharmacological inhibitor JQ1 in H441-FL cells. Long-term three-dimensional low attachment cultures may become a useful method for investigating the mechanisms underlying metastasis mediated by decreased cell-substratum adhesion.
Symptomatic extralobar pulmonary sequestration (EPS) is extremely rare. Herein, we report two male patients (3 and 16 years of age) with EPS presenting as hemothorax. Thoracotomic resections of the sequestrated lungs were uneventful. Pathologic examinations revealed hemothorax caused by circulatory disorders within the EPSs.
A 49-year-old woman with a 20-year history of Sjögren's syndrome (SS) was incidentally found to have an abnormal chest X-ray along with dyspnea and desaturation. Chest CT findings showed multiple cystic shadows, ground glass opacity, and small nodule-like lymphocytic interstitial pneumonia (LIP), which have been previously reported. She was diagnosed by surgical lung biopsy to have mucosa-associated lymphoid tissue (MALT) lymphoma. It was difficult to detect the presence of lymphoma by the use of only CT findings. Pulmonary involvement of SS occurs in various forms so that SS patients with pulmonary involvement should undergo open biopsy to reach a definitive diagnosis.
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