title: Melanoma tumors frequently acquire LRP2/megalin expression, which modulates melanoma cell proliferation and survival rates.
abstract: We show that the multiligand receptor megalin, known to mediate uptake and trafficking of nutrients and signaling molecules, is frequently expressed in malignant melanoma samples. Expression of megalin-encoding mRNA was investigated in 65 samples of nevi, melanomas, and melanoma metastases and was observed in more than 60% of the malignant samples, while only in 20% of the benign counterparts. Megalin expression in nevus and melanoma samples was additionally investigated by immunohistochemistry, which confirmed our mRNA-based observations. We furthermore show that a panel of tumor-derived melanoma cell lines express LRP2/megalin endogenously. In these cells, megalin is internalized from the cell surface and localizes extensively to intracellular vesicles, confirming receptor activity and pointing toward association with the endocytic apparatus. Groundbreaking, our results indicate that sustained megalin expression in melanoma cells is crucial for cell maintenance, as siRNA-mediated reduction in melanoma cell expression of LRP2/megalin significantly decreases melanoma cell proliferation and survival rates.
authors.affiliation: Department of Biomedicine, University of Aarhus, Aarhus, Denmark.
authors.forename: Rikke K
authors.initials: RK
authors.lastname: Andersen
authors.forename: Katrine
authors.initials: K
authors.lastname: Hammer
authors.forename: Henrik
authors.initials: H
authors.lastname: Hager
authors.forename: Julie N
authors.initials: JN
authors.lastname: Christensen
authors.forename: Maja
authors.initials: M
authors.lastname: Ludvigsen
authors.forename: Bent
authors.initials: B
authors.lastname: Honoré
authors.forename: Mai-Britt H
authors.initials: MB
authors.lastname: Thomsen
authors.forename: Mette
authors.initials: M
authors.lastname: Madsen
mesh_terms: D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D015180:Electrophoresis, Gel, Two-Dimensional; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000235:genetics* / Q000378:metabolism; D008545:Melanoma / Q000235:genetics* / Q000473:pathology*; D009362:Neoplasm Metastasis; D009506:Nevus / Q000235:genetics / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology*; D000096142:Cutaneous Malignant Melanoma
chemical_list: D026561:Low Density Lipoprotein Receptor-Related Protein-2; D012333:RNA, Messenger; D034741:RNA, Small Interfering
keywords: LRP2; megalin; melanoma; proliferation; survival