Martin Q. Rasmussen, Marie L. Bønnelykke-Behrndtz, Camilla Merrild, Ida Tvilling, Julie N. Christensen, Morten M. Nielsen, Jeanette B. Georgsen, Nina Naumann, Johann M. Gudbergsson, Anders Etzerodt, Jakob S. Pedersen, Russell W. Jenkins, Søren E. Degn, Søren K. Moestrup, Henrik Schmidt, Torben Steiniche, Mette Madsen
{"title":"LRP2在黑色素瘤中的表达与短暂细胞状态、T细胞浸润增加以及IFNy信号的上调有关","authors":"Martin Q. Rasmussen, Marie L. Bønnelykke-Behrndtz, Camilla Merrild, Ida Tvilling, Julie N. Christensen, Morten M. Nielsen, Jeanette B. Georgsen, Nina Naumann, Johann M. Gudbergsson, Anders Etzerodt, Jakob S. Pedersen, Russell W. Jenkins, Søren E. Degn, Søren K. Moestrup, Henrik Schmidt, Torben Steiniche, Mette Madsen","doi":"10.1111/pcmr.70053","DOIUrl":null,"url":null,"abstract":"<p>Low density lipoprotein receptor-related protein 2 (LRP2) is a 600 kilodalton multi-ligand endocytic membrane receptor expressed in several cell types during fetal development, including neuroepithelial cells, and in select absorptive epithelial cells in the adult. In epithelial cancers, LRP2 expression is associated with a differentiated tumor cell state and better prognosis. In previous work, we found that while LRP2 is not expressed in benign naevi, it is frequently acquired in melanoma. However, the molecular drivers of LRP2 expression in melanoma and characteristics of LRP2-expressing melanoma have yet to be described. Here, we show that LRP2 expression is related to a transitory melanoma cell state defined by co-expression of melanocyte lineage and neural crest transcriptional programs. Further, we reveal that melanoma LRP2 expression is increased in T cell-inflamed tumors and is directly upregulated through interferon-gamma signaling. Correlation of melanoma LRP2 expression with clinicopathological variables demonstrates that LRP2 expression is associated with low Breslow thickness and low clinical stage in primary melanomas. Taken together, the present study describes the characteristics of LRP2-expressing melanoma and reveals interferon-gamma signaling as a novel strong positive regulator of LRP2 expression in melanoma.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"38 5","pages":""},"PeriodicalIF":2.6000,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/pcmr.70053","citationCount":"0","resultStr":"{\"title\":\"LRP2 Expression in Melanoma Is Associated With a Transitory Cell State, Increased T Cell Infiltration, and Is Upregulated by IFNy Signaling\",\"authors\":\"Martin Q. Rasmussen, Marie L. Bønnelykke-Behrndtz, Camilla Merrild, Ida Tvilling, Julie N. Christensen, Morten M. Nielsen, Jeanette B. Georgsen, Nina Naumann, Johann M. Gudbergsson, Anders Etzerodt, Jakob S. Pedersen, Russell W. Jenkins, Søren E. Degn, Søren K. 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LRP2 Expression in Melanoma Is Associated With a Transitory Cell State, Increased T Cell Infiltration, and Is Upregulated by IFNy Signaling
Low density lipoprotein receptor-related protein 2 (LRP2) is a 600 kilodalton multi-ligand endocytic membrane receptor expressed in several cell types during fetal development, including neuroepithelial cells, and in select absorptive epithelial cells in the adult. In epithelial cancers, LRP2 expression is associated with a differentiated tumor cell state and better prognosis. In previous work, we found that while LRP2 is not expressed in benign naevi, it is frequently acquired in melanoma. However, the molecular drivers of LRP2 expression in melanoma and characteristics of LRP2-expressing melanoma have yet to be described. Here, we show that LRP2 expression is related to a transitory melanoma cell state defined by co-expression of melanocyte lineage and neural crest transcriptional programs. Further, we reveal that melanoma LRP2 expression is increased in T cell-inflamed tumors and is directly upregulated through interferon-gamma signaling. Correlation of melanoma LRP2 expression with clinicopathological variables demonstrates that LRP2 expression is associated with low Breslow thickness and low clinical stage in primary melanomas. Taken together, the present study describes the characteristics of LRP2-expressing melanoma and reveals interferon-gamma signaling as a novel strong positive regulator of LRP2 expression in melanoma.
期刊介绍:
Pigment Cell & Melanoma Researchpublishes manuscripts on all aspects of pigment cells including development, cell and molecular biology, genetics, diseases of pigment cells including melanoma. Papers that provide insights into the causes and progression of melanoma including the process of metastasis and invasion, proliferation, senescence, apoptosis or gene regulation are especially welcome, as are papers that use the melanocyte system to answer questions of general biological relevance. Papers that are purely descriptive or make only minor advances to our knowledge of pigment cells or melanoma in particular are not suitable for this journal. Keywords
Pigment Cell & Melanoma Research, cell biology, melatonin, biochemistry, chemistry, comparative biology, dermatology, developmental biology, genetics, hormones, intracellular signalling, melanoma, molecular biology, ocular and extracutaneous melanin, pharmacology, photobiology, physics, pigmentary disorders