Epithelial–mesenchymal Transition Phenotypes in Vertebral Metastases of Lung Cancer
| Autor: | Arvin H. Soepriatna, Gozde Uzunalli, L. Tiffany Lyle, Alexandra M. Dieterly, Craig J. Goergen, Chinyere M Kemet |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Male
Pathology medicine.medical_specialty Epithelial-Mesenchymal Transition Lung Neoplasms Mice Nude Toxicology Thoracic Vertebrae Pathology and Forensic Medicine Mice 03 medical and health sciences Cytokeratin 0302 clinical medicine Spinal cord compression Carcinoma Non-Small-Cell Lung medicine Animals Humans Epithelial–mesenchymal transition Lung cancer Molecular Biology 030304 developmental biology 0303 health sciences Spinal Neoplasms biology Brain Neoplasms business.industry CD44 Cancer Cell Biology medicine.disease medicine.anatomical_structure A549 Cells 030220 oncology & carcinogenesis Thoracic vertebrae biology.protein Adenocarcinoma Female business Neoplasm Transplantation |
| Zdroj: | Toxicologic Pathology. 47:515-527 |
| ISSN: | 1533-1601 0192-6233 |
| Popis: | Vertebral metastases of non-small cell lung cancer (NSCLC) are frequently diagnosed in the metastatic setting and are commonly identified in the thoracic vertebrae in patients. Treatment of NSCLC bone metastases, which are often multiple, is palliative, and the median survival times are 3 to 6 months. We have characterized spontaneous vertebral metastases in a brain metastases model of NSCLC and correlated these findings with epithelial–mesenchymal transition (EMT). Brain metastases were established in athymic nude mice following intracardiac injection of brain-seeking adenocarcinoma NSCLC cells. Thirty-nine percent of mice (14/36) developed spontaneous vertebral metastases, spinal cord compression, and hind-limb paralysis. Vertebral metastases consisted of an adenocarcinoma phenotype with neoplastic epithelial cells arranged in cords or acini and a mesenchymal phenotype with spindloid neoplastic cells arranged in bundles and streams. Quantitative and qualitative immunohistochemical and immunofluorescence assays demonstrated an increase in vimentin expression compared to cytokeratin expression in vertebral metastases. A correlation with EMT was supported by an increase in CD44 in vertebral metastases and parenchymal metastases. These data demonstrate a translational lung cancer metastasis model with spontaneous vertebral metastasis. The mesenchymal and epithelial phenotype of these spontaneous metastases coupled with EMT provide a conduit to improve drug delivery and overall patient survival. |
| Databáze: | OpenAIRE |
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