The shedded ectodomain of Lyve-1 expressed on M2-like tumorassociated macrophages inhibits melanoma cell proliferation
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The shedded ectodomain of Lyve-1 expressed on M2-like tumorassociated macrophages inhibits melanoma cell proliferation. / Dollt, Claudia; Becker, Kathrin; Michel, Julia; Melchers, Susanne; Weis, Cleo-Aron; Schledzewski, Kai; Krewer, Andreas; Kloss, Loreen; Gebhardt, Christoffer; Utikal, Jochen; Schmieder, Astrid.
in: ONCOTARGET, Jahrgang 8, Nr. 61, 28.11.2017, S. 103682-103692.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - The shedded ectodomain of Lyve-1 expressed on M2-like tumorassociated macrophages inhibits melanoma cell proliferation
AU - Dollt, Claudia
AU - Becker, Kathrin
AU - Michel, Julia
AU - Melchers, Susanne
AU - Weis, Cleo-Aron
AU - Schledzewski, Kai
AU - Krewer, Andreas
AU - Kloss, Loreen
AU - Gebhardt, Christoffer
AU - Utikal, Jochen
AU - Schmieder, Astrid
PY - 2017/11/28
Y1 - 2017/11/28
N2 - 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 low-molecular 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 inLyve-1knockout 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 co-express 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.
AB - 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 low-molecular 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 inLyve-1knockout 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 co-express 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.
KW - Journal Article
UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-85035327200&partnerID=MN8TOARS
U2 - 10.18632/oncotarget.21771
DO - 10.18632/oncotarget.21771
M3 - SCORING: Journal article
C2 - 29262593
VL - 8
SP - 103682
EP - 103692
JO - ONCOTARGET
JF - ONCOTARGET
SN - 1949-2553
IS - 61
ER -
