title: Melanoma exosome induction of endothelial cell GM-CSF in pre-metastatic lymph nodes may result in different M1 and M2 macrophage mediated angiogenic processes.
abstract: Angiogenesis is a key process in the preparation of lymph nodes for melanoma metastasis. Granulocyte macrophage colony stimulating factor (GM-CSF) induces hypoxia inducible factor 1 alpha (HIF-1α) in M1 or HIF-2α in M2 polarized macrophages. HIF-1α promotes neoangiogenesis while HIF-2α facilitates morphogenic normalization of neovasculature. Melanoma exosomes induce GM-CSF expression by endothelial cells in vitro and HIF-1α expression in pre-metastatic lymph nodes in vivo. This suggest a relationship between melanoma exosome induced endothelial GM-CSF and macrophage mediated angiogenesis in lymph nodes. Theoretically, induction of endothelial cell derived GM-CSF by melanoma exosomes mediates different angiogenic functions in pre-metastatic lymph nodes depending on subcapsular sinus (SCS) macrophage polarity. To explore this hypothesis, experiments utilizing melanoma exosomes in a lymph node model are outlined. Despite their opposing immune functions, indirect melanoma exosome stimulation of M1 or M2 SCS macrophages via endothelial derived GM-CSF in lymph nodes may induce different although complementary pro-tumor angiogenic processes.
authors: University of Louisville, Department of Pharmacology and Toxicology and The James Graham Brown Cancer Center, Clinical and Translational Research Building, 505 South Hancock Street, Louisville, KY 40202, United States. Electronic address: joshua.hood@louisville.edu.
authors: Joshua L
authors: JL
authors: Hood
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism*; D055354:Exosomes / Q000378:metabolism*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007107:Immune System; D016753:Interleukin-10 / Q000378:metabolism; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism*; D051379:Mice; D008962:Models, Theoretical; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic; D018919:Neovascularization, Physiologic; D063267:Sialic Acid Binding Ig-like Lectin 1 / Q000378:metabolism; D015398:Signal Transduction; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D000951:Antigens, Neoplasm; D051792:Basic Helix-Loop-Helix Proteins; D016207:Cytokines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016753:Interleukin-10; D063267:Sialic Acid Binding Ig-like Lectin 1; D000099162:Endothelial PAS Domain-Containing Protein 1; C497442:HIF1A protein, human