2. Academic Validation
  3. GPNMB marks a quiescent cell population in melanoma and promotes metastasis formation

GPNMB marks a quiescent cell population in melanoma and promotes metastasis formation

  • EMBO Rep. 2025 Jun 17. doi: 10.1038/s44319-025-00501-w.
Fiorenza Lotti 1,  Marine Melixetian 1,  Thalia Vlachou 1 2,  Marco S Nobile 3,  Leone Bacciu 3,  Marco Malferrari 4,  Nicolò Quaresima 4,  Stefania Rapino 4,  Federica Marocchi 1,  Massimo Barberis 1,  Chiara Soriani 1,  Barbara Gallo 1,  Velia Mollo 1,  Ilaria Ferrarotto 1,  Daniela Bossi 1 5,  Pier Francesco Ferrucci 1 6,  Pier Giuseppe Pelicci 1 7,  Lucilla Luzi 1,  Luisa Lanfrancone 8
Affiliations

Affiliations

  • 1 Department of Experimental Oncology, European Institute of Oncology IRCCS, Milan, Italy.
  • 2 Purposeful, Tritis Septembriou 144, Athens, 11251, Greece.
  • 3 Department of Environmental Science, Computer Science and Statistics, University of Ca' Foscari, Venice, Italy.
  • 4 Department of Chemistry "Giacomo Ciamician", Università di Bologna, Via Selmi 2, 40126, Bologna, Italy.
  • 5 Institute of Oncology Research, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
  • 6 Department of Oncology, Gruppo MultiMedica, Milano, Italy.
  • 7 Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, Milan, Italy.
  • 8 Department of Experimental Oncology, European Institute of Oncology IRCCS, Milan, Italy. luisa.lanfrancone@ieo.it.
PMID: 40528051 DOI: 10.1038/s44319-025-00501-w
Abstract

Melanoma exhibits high intratumoral heterogeneity, characterized by a diverse population of cells undergoing dynamic transitions between cellular states. These adaptive changes enable melanoma cells to survive in the harsh tumor microenvironment, acquire drug resistance, and metastasize. One such state, quiescence, has been linked to both relapse and drug resistance, but its underlying biology and molecular mechanisms remain poorly understood. Our study challenges the conventional understanding of melanoma quiescence. Contrary to the notion of a rare, unique subpopulation, we demonstrate that quiescence is a highly dynamic state accessible to most, if not all, melanoma cells. This state is exquisitely sensitive to microenvironmental cues. We identify GPNMB as a marker of quiescence, that is expressed in both primary and metastatic tumors. GPNMB-positive cells exhibit a pro-metastatic phenotype and are enriched in metastatic sites, suggesting a potential role for quiescence in tumor dissemination. Our findings position GPNMB as a valuable marker for isolating quiescent melanoma cells and as a potential therapeutic target to tackle metastasis.

Keywords

Hypoxia; Melanoma; Metastasis; Quiescence; Target Therapy.

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