title: Metastatic potential of B16-F10 melanoma cells is enhanced by extracellular S100A4 derived from RAW264.7 macrophages.
abstract: S100A4, synthesized and secreted from both tumor and stroma cells, modulates an aggressive tumor phenotype in various cancers by intracellular and extracellular interactions which are not completely understood. Because of the high content of tumor-associated macrophages in melanoma, here, a syngeneic model (coculture of mouse B16-F10 melanoma cells (Mel) and RAW264.7 macrophages (Mϕ); administration (i.v.) of Mel and Mϕ/Mel in NMRI nu/nu mice) was used to investigate synthesis and secretion of (a) S100A4, (b) S100A4-mediated signaling and activation of NFκB, and (c) S100A4-mediated modulation of Mel invasiveness in vitro (transwell assay, transwell matrigel assay) and in vivo (metastatic lung colonization), respectively. In this model substantial S100A4 synthesis and secretion is demonstrated in Mϕ. Macrophage-derived S100A4 promotes Mel invasiveness in a paracrine manner in vitro, which is further substantiated in control experiments using recombinant human S100A4 and Mel stably transfected with mouse S100A4. Moreover, the participation of S100A4-mediated signaling, e.g., via the receptor for advanced glycation endproducts (RAGE), resulting in activation of NFκB was demonstrated in all experimental settings. Finally, we demonstrated that interaction of macrophage-derived S100A4 with Mel results in increased metastatic lung colonization in vivo.
authors.affiliation: Department Radiopharmaceutical and Chemical Biology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany. Electronic address: c.haase@hzdr.de.
authors.forename: Cathleen
authors.initials: C
authors.lastname: Haase-Kohn
authors.affiliation: Department Radiopharmaceutical and Chemical Biology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany; Department of Chemistry and Food Chemistry, Technische Universität Dresden, Dresden, Germany.
authors.forename: Susann
authors.initials: S
authors.lastname: Wolf
authors.affiliation: Department Radiopharmaceutical and Chemical Biology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany; Department of Chemistry and Food Chemistry, Technische Universität Dresden, Dresden, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Herwig
authors.affiliation: Department Radiopharmaceutical and Chemical Biology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Mosch
authors.affiliation: Department Radiopharmaceutical and Chemical Biology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany; Department of Chemistry and Food Chemistry, Technische Universität Dresden, Dresden, Germany. Electronic address: j.pietzsch@hzdr.de.
authors.forename: Jens
authors.initials: J
authors.lastname: Pietzsch
mesh_terms: D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D008264:Macrophages / Q000378:metabolism*; D008546:Melanoma, Experimental / Q000378:metabolism* / Q000473:pathology / Q000556:secondary*; D051379:Mice; D008819:Mice, Nude; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D016328:NF-kappa B; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C470944:S100a4 protein, mouse
keywords: Melanoma metastasis; Receptor for advanced glycation endproducts (RAGE); S100 proteins; Tumor-associated macrophages (TAM)