{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T05:26:32Z","timestamp":1784697992302,"version":"3.55.0"},"reference-count":53,"publisher":"Bioscientifica","issue":"6","content-domain":{"domain":["erc.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,4,11]]},"abstract":"<jats:p>\n                    Lymphangioleiomyomatosis (LAM) is a rare, progressive cystic lung disease affecting almost exclusively female-sexed individuals. The cysts represent regions of lung destruction caused by smooth muscle tumors containing mutations in one of the two tuberous sclerosis (\n                    <jats:italic>TSC<\/jats:italic>\n                    ) genes. mTORC1 inhibition slows but does not stop LAM advancement. Furthermore, monitoring disease progression is hindered by insufficient biomarkers. Therefore, new treatment options and biomarkers are needed. LAM cells express melanocytic markers, including glycoprotein non-metastatic melanoma protein B (GPNMB). The function of GPNMB in LAM is currently unknown; however, GPNMB\u2019s unique cell surface expression on tumor versus benign cells makes GPNMB a potential therapeutic target, and persistent release of its extracellular ectodomain suggests potential as a serum biomarker. Here, we establish that GPNMB expression is dependent on mTORC1 signaling, and that GPNMB regulates TSC2-null tumor cell invasion\n                    <jats:italic>in vitro<\/jats:italic>\n                    . Further, we demonstrate that GPNMB enhances TSC2-null xenograft tumor growth\n                    <jats:italic>in vivo<\/jats:italic>\n                    , and that ectodomain release is required for this xenograft growth. We also show that GPNMB\u2019s ectodomain is released from the cell surface of TSC2-null cells by proteases ADAM10 and 17, and we identify the protease target sequence on GPNMB. Finally, we demonstrate that GPNMB\u2019s ectodomain is present at higher levels in LAM patient serum compared to healthy controls and that ectodomain levels decrease with mTORC1 inhibition, making it a potential LAM biomarker.\n                  <\/jats:p>","DOI":"10.1530\/erc-23-0312","type":"journal-article","created":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T11:53:02Z","timestamp":1713268382000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-8","source":"Crossref","is-referenced-by-count":17,"title":["Glycoprotein non-metastatic melanoma protein B promotes tumor growth and is a biomarker for lymphangioleiomyomatosis"],"prefix":"10.1530","volume":"31","author":[{"given":"Erin","family":"Gibbons","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology University of Rochester School of Medicine and Dentistry, Rochester, New York, USA"},{"name":"Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manisha","family":"Taya","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, UT Southwestern, Dallas, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huixing","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care and Sleep Medicine, University of Cincinnati, Cincinnati, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samia H","family":"Lopa","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Computational Biology, University of Rochester, Rochester, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Moss","sequence":"additional","affiliation":[{"name":"Pulmonary Branch, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth P","family":"Henske","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis X","family":"McCormack","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care and Sleep Medicine, University of Cincinnati, Cincinnati, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7367-276X","authenticated-orcid":true,"given":"Stephen R","family":"Hammes","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology University of Rochester School of Medicine and Dentistry, Rochester, New York, USA"},{"name":"Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"bib1","series-title":"Alzheimer\u2019s Research and Therapy","first-page":"94","article-title":"Evaluation of cerebrospinal fluid glycoprotein NMB (GPNMB) as a potential biomarker for Alzheimer's disease","volume":"13","author":"Aichholzer","year":"2021","unstructured":"Aichholzer FKlafki HWOgorek IVogelgsang JWiltfang JScherbaum NWeggen S & Wirths O2021Evaluation of cerebrospinal fluid glycoprotein NMB (GPNMB) as a potential biomarker for Alzheimer's disease. 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