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The shedded ectodomain of Lyve-1 expressed on M2-like tumor-associated macrophages inhibits melanoma cell proliferation

Targeting immune cells that support tumor growth is an effective therapeutic strategy in tumor entities such as melanoma. M2-like tumor-associated macrophages (TAM) sustain tumor growth by secreting anti-inflammatory cytokines, proteases and growth factors. In this study, we show that a protein deri...

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Main Authors: Dollt, Claudia (Author) , Becker, Kathrin (Author) , Michel, Julia (Author) , Melchers, Susanne (Author) , Weis, Cleo-Aron Thias (Author) , Schledzewski, Kai (Author) , Krewer, Andreas (Author) , Kloss, Loreen (Author) , Gebhardt, Christoffer (Author) , Utikal, Jochen (Author) , Schmieder, Astrid (Author)
Format: Article (Journal)
Language:English
Published: October 10, 2017
In: OncoTarget
Year: 2017, Volume: 8, Issue: 61, Pages: 103682-103692
ISSN:1949-2553
DOI:10.18632/oncotarget.21771
Online Access:Verlag, Volltext: http://dx.doi.org/10.18632/oncotarget.21771
Verlag, Volltext: http://www.oncotarget.com/fulltext/21771
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Author Notes:Claudia Dollt, Kathrin Becker, Julia Michel, Susanne Melchers, Cleo-Aron Weis, Kai Schledzewski, Andreas Krewer, Loreen Kloss, Christoffer Gebhardt, Jochen Utikal and Astrid Schmieder
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Summary:Targeting immune cells that support tumor growth is an effective therapeutic strategy in tumor entities such as melanoma. M2-like tumor-associated macrophages (TAM) sustain tumor growth by secreting anti-inflammatory cytokines, proteases and growth factors. In this study, we show that a protein derived from M2-like macrophages namely the shedded ectodomain of Lyve-1 (sLyve-1) decreases human HT144 and murine B16F1 melanoma cell proliferation significantly by acting as a decoy receptor for lowmolecular weight hyaluronic acid (LMW-HA) although the LMW-HA/Lyve-1 interaction on lymphatic endothelial cells has been described to induce lymphangiogenesis. This is in line with our finding that the number of LYVE-1+ TAM decreases in higher human melanoma stages and that the early growth of B16 transplant tumors is enhanced in Lyve-1 knockout mice when compared to wild-type mice due to an increased melanoma cell proliferation. LYVE-1 expressing TAM are however true M2 macrophages as they coexpress typical M2-markers such as CD163 and CD206. The results of the present study highlight the necessity to carefully determine the net effect particular TAM subpopulations have on tumors before establishing a treatment to target these immune cells.
Item Description:Gesehen am 12.07.2018
Physical Description:Online Resource
ISSN:1949-2553
DOI:10.18632/oncotarget.21771

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