Age-Related Increases in IGFBP2 Increase Melanoma Cell Invasion and Lipid Synthesis.

Autor:	Alicea GM; Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.; Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, Maryland., Patel P; Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, Maryland., Portuallo ME; Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland., Fane ME; Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.; The Fox Chase Cancer Center, Philadelphia, Pennsylvania., Wei M; Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland., Chhabra Y; Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.; The Fox Chase Cancer Center, Philadelphia, Pennsylvania., Dixit A; Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland., Carey AE; Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland., Wang V; Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland., Rocha MR; Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland., Behera R; The Wistar Institute, Philadelphia, Pennsylvania., Speicher DW; The Wistar Institute, Philadelphia, Pennsylvania., Tang HY; The Wistar Institute, Philadelphia, Pennsylvania., Kossenkov AV; The Wistar Institute, Philadelphia, Pennsylvania., Rebecca VW; Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland., Wirtz D; Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, Maryland.; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland., Weeraratna AT; Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Jazyk:	angličtina
Zdroj:	Cancer research communications [Cancer Res Commun] 2024 Aug 01; Vol. 4 (8), pp. 1908-1918.
DOI:	10.1158/2767-9764.CRC-23-0176
Abstrakt:	Aged patients with melanoma (>65 years old) have more aggressive disease relative to young patients (<55 years old) for reasons that are not completely understood. Analysis of the young and aged secretome from human dermal fibroblasts identified >5-fold levels of IGF-binding protein 2 (IGFBP2) in the aged fibroblast secretome. IGFBP2 functionally triggers upregulation of the PI3K-dependent fatty acid biosynthesis program in melanoma cells. Melanoma cells co-cultured with aged dermal fibroblasts have higher levels of lipids relative to those co-cultured with young dermal fibroblasts, which can be lowered by silencing IGFBP2 expression in fibroblasts prior to treating with conditioned media. Conversely, ectopically treating melanoma cells with recombinant IGFBP2 in the presence of conditioned media from young fibroblasts or overexpressing IGFBP2 in melanoma cells promoted lipid synthesis and accumulation in melanoma cells. Treatment of young mice with rIGFBP2 increases tumor growth. Neutralizing IGFBP2 in vitro reduces migration and invasion in melanoma cells, and in vivo studies demonstrate that neutralizing IGFBP2 in syngeneic aged mice reduces tumor growth and metastasis. Our results suggest that aged dermal fibroblasts increase melanoma cell aggressiveness through increased secretion of IGFBP2, stressing the importance of considering age when designing studies and treatment. Significance: The aged microenvironment drives metastasis in melanoma cells. This study reports that IGFBP2 secretion by aged fibroblasts induces lipid accumulation in melanoma cells, driving an increase in tumor invasiveness. Neutralizing IGFBP2 decreases melanoma tumor growth and metastasis. (©2024 The Authors; Published by the American Association for Cancer Research.)
Databáze:	MEDLINE
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