| First Author | Zhao T | Year | 2016 |
| Journal | Am J Pathol | Volume | 186 |
| Issue | 8 | Pages | 2183-2192 |
| PubMed ID | 27461363 | Mgi Jnum | J:235286 |
| Mgi Id | MGI:5796043 | Doi | 10.1016/j.ajpath.2016.04.014 |
| Citation | Zhao T, et al. (2016) Lung Epithelial Cell-Specific Expression of Human Lysosomal Acid Lipase Ameliorates Lung Inflammation and Tumor Metastasis in Lipa(-/-) Mice. Am J Pathol 186(8):2183-92 |
| abstractText | 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. |
