Lung Epithelial Cell–Specific Expression of Human Lysosomal Acid Lipase Ameliorates Lung Inflammation and Tumor Metastasis in Lipa−/− Mice
dc.contributor.author | Zhao, Ting | |
dc.contributor.author | Ding, Xinchun | |
dc.contributor.author | Du, Hong | |
dc.contributor.author | Yan, Cong | |
dc.contributor.department | Pathology and Laboratory Medicine, School of Medicine | en_US |
dc.date.accessioned | 2018-02-20T19:17:00Z | |
dc.date.available | 2018-02-20T19:17:00Z | |
dc.date.issued | 2016-08 | |
dc.description.abstract | Lysosomal acid lipase (LAL), a key enzyme in the metabolic pathway of neutral lipids, has a close connection with inflammation and tumor progression. One major manifestation in LAL-deficient (Lipa−/−) mice is an increase of tumor growth and metastasis associated with expansion of myeloid-derived suppressor cells. In the lung, LAL is highly expressed in alveolar type II epithelial cells. To assess how LAL in lung epithelial cells plays a role in this inflammation-related pathogenic process, lung alveolar type II epithelial cell–specific expression of human LAL (hLAL) in Lipa−/− mice was established by crossbreeding of CCSP-driven rtTA transgene and (TetO)7-CMV-hLAL transgene into Lipa−/− mice (CCSP-Tg/KO). hLAL expression in lung epithelial cells not only reduced tumor-promoting myeloid-derived suppressor cells in the lung, but also down-regulated the synthesis and secretion of tumor-promoting cytokines and chemokines into the bronchoalveolar lavage fluid of Lipa−/− mice. hLAL expression reduced the immunosuppressive functions of bronchoalveolar lavage fluid cells, inhibited bone marrow cell transendothelial migration, and inhibited endothelial cell proliferation and migration in Lipa−/− mice. As a result, hLAL expression in CCSP-Tg/KO mice corrected pulmonary damage, and inhibited tumor cell proliferation and migration in vitro, and tumor metastasis to the lung in vivo. These results support a concept that LAL is a critical metabolic enzyme in lung epithelial cells that regulates lung homeostasis, immune response, and tumor metastasis. | en_US |
dc.eprint.version | Final published version | en_US |
dc.identifier.citation | Zhao, T., Ding, X., Du, H., & Yan, C. (2016). Lung Epithelial Cell–Specific Expression of Human Lysosomal Acid Lipase Ameliorates Lung Inflammation and Tumor Metastasis in Lipa−/− Mice. The American Journal of Pathology, 186(8), 2183–2192. https://doi.org/10.1016/j.ajpath.2016.04.014 | en_US |
dc.identifier.uri | https://hdl.handle.net/1805/15252 | |
dc.publisher | Elsevier | en_US |
dc.relation.isversionof | 10.1016/j.ajpath.2016.04.014 | en_US |
dc.relation.journal | The American Journal of Pathology | en_US |
dc.source | PMC | en_US |
dc.subject | Alveolar Epithelial Cells | en_US |
dc.subject | Neoplasm Metastasis | en_US |
dc.subject | Pneumonia | en_US |
dc.subject | Sterol Esterase | en_US |
dc.title | Lung Epithelial Cell–Specific Expression of Human Lysosomal Acid Lipase Ameliorates Lung Inflammation and Tumor Metastasis in Lipa−/− Mice | en_US |
dc.type | Article | en_US |
ul.alternative.fulltext | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4973654/ | en_US |