Your browser doesn't support javascript.
loading
Glycoprotein non-metastatic melanoma protein B promotes tumor growth and is a biomarker for lymphangioleiomyomatosis.
Gibbons, Erin; Taya, Manisha; Wu, Huixing; Lopa, Samia H; Moss, Joel; Henske, Elizabeth P; McCormack, Francis X; Hammes, Stephen R.
Afiliación
  • Gibbons E; Department of Microbiology and Immunology University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.
  • Taya M; Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.
  • Wu H; Division of Hematology and Oncology, UT Southwestern, Dallas, Texas, USA.
  • Lopa SH; Division of Pulmonary, Critical Care and Sleep Medicine, University of Cincinnati, Cincinnati, Ohio, USA.
  • Moss J; Department of Biostatistics and Computational Biology, University of Rochester, Rochester, New York, USA.
  • Henske EP; Pulmonary Branch, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, Maryland, USA.
  • McCormack FX; Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
  • Hammes SR; Division of Pulmonary, Critical Care and Sleep Medicine, University of Cincinnati, Cincinnati, Ohio, USA.
Endocr Relat Cancer ; 31(6)2024 Jun 01.
Article en En | MEDLINE | ID: mdl-38614127
ABSTRACT
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 (TSC) 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's 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 in vitro. Further, we demonstrate that GPNMB enhances TSC2-null xenograft tumor growth in vivo, and that ectodomain release is required for this xenograft growth. We also show that GPNMB's 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's 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.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Glicoproteínas de Membrana / Biomarcadores de Tumor / Linfangioleiomiomatosis Límite: Animals / Female / Humans Idioma: En Revista: Endocr Relat Cancer Asunto de la revista: ENDOCRINOLOGIA / NEOPLASIAS Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Glicoproteínas de Membrana / Biomarcadores de Tumor / Linfangioleiomiomatosis Límite: Animals / Female / Humans Idioma: En Revista: Endocr Relat Cancer Asunto de la revista: ENDOCRINOLOGIA / NEOPLASIAS Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido