Lymphangioleiomyomatosis: a metastatic lung disease

• Published in: American Journal of Physiology: Cell Physiology Vol. 324; no. 2; pp. C320 - C326
• Main Authors: Kundu, Nandini, Holz, Marina K
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.02.2023
• Series: Tumor Host Interactions in Metastasis
• Subjects: Cell signaling; Estrogens; Female; Humans; Immune system; Lung - metabolism; Lung diseases; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lymphangioleiomyomatosis - genetics; Lymphangioleiomyomatosis - metabolism; Lymphangioleiomyomatosis - pathology; Mesenchyme; Metastases; Rapamycin; Review; Tuberous Sclerosis Complex 1; Tuberous Sclerosis Complex 2; Tuberous Sclerosis Complex 2 Protein - metabolism; Tumor Microenvironment; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism; Tumors; lung; mTOR; rare disease; TSC; lymphangioleiomyomatosis
• ISSN: 0363-6143; 1522-1563
• DOI: 10.1152/ajpcell.00202.2022

Lymphangioleiomyomatosis (LAM) is a rare disease affecting women, caused by somatic mutations in the TSC1 or TSC2 genes, and driven by estrogen. Similar to many cancers, it is metastatic, primarily to the lung. Despite its monogenetic nature, like many cancers, LAM is a heterogeneous disease. The cellular constituents of LAM are very diverse, including mesenchymal, epithelial, endothelial, and immune cells. LAM is characterized by dysregulation of many cell signaling pathways, distinct populations of LAM cells, and a rich microenvironment, in which the immune system appears to play an important role. This review delineates the heterogeneity of LAM and focuses on the metastatic features of LAM, the deregulated signaling mechanisms and the tumor microenvironment. Understanding the tumor-host interaction in LAM may provide insights into the development of new therapeutic strategies, which could be combinatorial or superlative to Sirolimus, the current U.S. Food and Drug Administration-approved treatment.