ArticleEndocrine-related cancer2016
Estrogen maintains myometrial tumors in a lymphangioleiomyomatosis model.
Article in Endocrine-related cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 38 citations in OpenAlex.
- mTORC1 activation induces B7-H3-dependent metabolic reprogramming in renal cell carcinoma (RCC).Oncogene · 2026Article
- Intersecting Roles of Estrogens and Neutrophils in Modulating Innate Immunity in Cancer.Biomolecules · 2026Review
- GPNMB immunohistochemistry is a useful ancillary tool for the diagnosis of pulmonary lymphangioleiomyomatosis.Histopathology · 2026Article
- Exploring the Role of Neutrophils in Pathogenesis of Lymphangioleiomyomatosis.Journal of innate immunity · 2026Review
- Macrophages lacking TSC2 have mTORC1-dependent increased GPNMB and ameliorate ventricular dysfunction/remodeling after ischemia-reperfusion.Scientific reports · 2025Article
- Addressing Sex as a Biological Variable in Preclinical Models of Lung Disease: An Official American Thoracic Society Research Statement.American journal of respiratory and critical care medicine · 2025Article
- Inflammatory, Functional, and Compositional Changes of the Uterine Immune Microenvironment in a Lymphangioleiomyomatosis Mouse Model.Journal of cellular immunology · 2025Article
- STAT1 Promotes PD-L1 Activation and Tumor Growth in Lymphangioleiomyomatosis.bioRxiv : the preprint server for biology · 2024Article
- The development for emerging biomarkers of lymphangioleiomyomatosis.Orphanet journal of rare diseases · 2024Review
- Glycoprotein non-metastatic melanoma protein B promotes tumor growth and is a biomarker for lymphangioleiomyomatosis.Endocrine-related cancer · 2024Article
- Lymphangioleiomyomatosis: where endocrinology, immunology and tumor biology meet.Endocrine-related cancer · 2023Review
- Lymphangioleiomyomatosis and Other Cystic Lung Diseases.Immunology and allergy clinics of North America · 2023Review
- Estradiol Augments Tumor-Induced Neutrophil Production to Promote Tumor Cell Actions in Lymphangioleiomyomatosis Models.Endocrinology · 2023Article
- An Evidence-Based Update on the Potential Association between Rheumatoid Arthritis and Lymphangioleiomyomatosis.Journal of personalized medicine · 2023Review
- Prolactin is Expressed in Uterine Leiomyomas and Promotes Signaling and Fibrosis in Myometrial Cells.Reproductive sciences (Thousand Oaks, Calif.) · 2022Article
- GPNMB expression identifies TSC1/2/mTOR-associated and MiT family translocation-driven renal neoplasms.The Journal of pathology · 2022Article
- Article
- Tuberous sclerosis complex for the pulmonologist.European respiratory review : an official journal of the European Respiratory Society · 2021Article
- Sex-Steroid Signaling in Lung Diseases and Inflammation.Advances in experimental medicine and biology · 2021Article
- Single-Cell Transcriptomic Analysis Identifies a Unique Pulmonary Lymphangioleiomyomatosis Cell.American journal of respiratory and critical care medicine · 2020Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Lymphangioleiomyomatosis (LAM) is a rare disease in women. Patients with LAM develop metastatic smooth-muscle cell adenomas within the lungs, resulting in reduced pulmonary function. LAM cells contain mutations in tuberous sclerosis genes (TSC1 or TSC2), leading to up-regulation of mTORC1 activity and elevated proliferation. The origin of LAM cells remains unknown; however, inactivation of Tsc2 gene in the mouse uterus resulted in myometrial tumors exhibiting LAM features, and approximately 50% of animals developed metastatic myometrial lung tumors. This suggests that LAM tumors might originate from the uterine myometrium, possibly explaining the overwhelming prevalence of LAM in female. Here, we demonstrate that mouse Tsc2-null myometrial tumors exhibit nearly all the features of LAM, including mTORC1/S6K activation, as well as expression of melanocytic markers and matrix metalloproteinases (MMPs). Estrogen ablation reduces S6K signaling and results in Tsc2-null myometrial tumor regression. Thus, even without TSC2, estradiol is required to maintain tumors and mTORC1/S6K signaling. Additionally, we find that MMP-2 and -9, as well as neutrophil elastase (NE), are overexpressed in Tsc2-null myometrial tumors in an estrogen-dependent fashion. In vivo fluorescent imaging using MMP- or NE-sensitive optical biomarkers confirms that protease activity is specific to myometrial tumors. Similar to LAM cells, uterine Tsc2-null myometrial cells also overexpress melanocytic markers in an estrogen-dependent fashion. Finally, we identify glycoprotein NMB (GPNMB) as a melanocytic marker up-regulated in Tsc2-null mouse uteri and human LAM samples. Our data highlight the potential importance of estradiol in LAM cells, suggesting that anti-estrogen therapy may be a treatment modality. Furthermore, proteases and GPNMB might be useful LAM biomarkers.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.