2.50
Hdl Handle:
http://hdl.handle.net/10033/621004
Title:
Modulation of actin dynamics as potential macrophage subtype-targeting anti-tumour strategy.
Authors:
Pergola, Carlo; Schubert, Katrin; Pace, Simona; Ziereisen, Jana; Nikels, Felix; Scherer, Olga; Hüttel, Stephan; Zahler, Stefan; Vollmar, Angelika M; Weinigel, Christina; Rummler, Silke; Müller, Rolf ( 0000-0002-1042-5665 ) ; Raasch, Martin; Mosig, Alexander; Koeberle, Andreas; Werz, Oliver
Abstract:
Tumour-associated macrophages mainly comprise immunosuppressive M2 phenotypes that promote tumour progression besides anti-tumoural M1 subsets. Selective depletion or reprogramming of M2 may represent an innovative anti-cancer strategy. The actin cytoskeleton is central for cellular homeostasis and is targeted for anti-cancer chemotherapy. Here, we show that targeting G-actin nucleation using chondramide A (ChA) predominantly depletes human M2 while promoting the tumour-suppressive M1 phenotype. ChA reduced the viability of M2, with minor effects on M1, but increased tumour necrosis factor (TNF)α release from M1. Interestingly, ChA caused rapid disruption of dynamic F-actin filaments and polymerization of G-actin, followed by reduction of cell size, binucleation and cell division, without cellular collapse. In M1, but not in M2, ChA caused marked activation of SAPK/JNK and NFκB, with slight or no effects on Akt, STAT-1/-3, ERK-1/2, and p38 MAPK, seemingly accounting for the better survival of M1 and TNFα secretion. In a microfluidically-supported human tumour biochip model, circulating ChA-treated M1 markedly reduced tumour cell viability through enhanced release of TNFα. Together, ChA may cause an anti-tumoural microenvironment by depletion of M2 and activation of M1, suggesting induction of G-actin nucleation as potential strategy to target tumour-associated macrophages in addition to neoplastic cells.
Affiliation:
Helmholtz Institut für pharmazeutische Forschung Saarland, Universitätscampus E8.1, 66123 Saarbrücken, Germany.
Citation:
Modulation of actin dynamics as potential macrophage subtype-targeting anti-tumour strategy. 2017, 7:41434 Sci Rep
Journal:
Scientific reports
Issue Date:
30-Jan-2017
URI:
http://hdl.handle.net/10033/621004
DOI:
10.1038/srep41434
PubMed ID:
28134280
Type:
Article
Language:
en
ISSN:
2045-2322
Appears in Collections:
publications of the department of microbial natural substances ([HIPS]MINS)

Full metadata record

DC FieldValue Language
dc.contributor.authorPergola, Carloen
dc.contributor.authorSchubert, Katrinen
dc.contributor.authorPace, Simonaen
dc.contributor.authorZiereisen, Janaen
dc.contributor.authorNikels, Felixen
dc.contributor.authorScherer, Olgaen
dc.contributor.authorHüttel, Stephanen
dc.contributor.authorZahler, Stefanen
dc.contributor.authorVollmar, Angelika Men
dc.contributor.authorWeinigel, Christinaen
dc.contributor.authorRummler, Silkeen
dc.contributor.authorMüller, Rolfen
dc.contributor.authorRaasch, Martinen
dc.contributor.authorMosig, Alexanderen
dc.contributor.authorKoeberle, Andreasen
dc.contributor.authorWerz, Oliveren
dc.date.accessioned2017-07-11T10:05:51Z-
dc.date.available2017-07-11T10:05:51Z-
dc.date.issued2017-01-30-
dc.identifier.citationModulation of actin dynamics as potential macrophage subtype-targeting anti-tumour strategy. 2017, 7:41434 Sci Repen
dc.identifier.issn2045-2322-
dc.identifier.pmid28134280-
dc.identifier.doi10.1038/srep41434-
dc.identifier.urihttp://hdl.handle.net/10033/621004-
dc.description.abstractTumour-associated macrophages mainly comprise immunosuppressive M2 phenotypes that promote tumour progression besides anti-tumoural M1 subsets. Selective depletion or reprogramming of M2 may represent an innovative anti-cancer strategy. The actin cytoskeleton is central for cellular homeostasis and is targeted for anti-cancer chemotherapy. Here, we show that targeting G-actin nucleation using chondramide A (ChA) predominantly depletes human M2 while promoting the tumour-suppressive M1 phenotype. ChA reduced the viability of M2, with minor effects on M1, but increased tumour necrosis factor (TNF)α release from M1. Interestingly, ChA caused rapid disruption of dynamic F-actin filaments and polymerization of G-actin, followed by reduction of cell size, binucleation and cell division, without cellular collapse. In M1, but not in M2, ChA caused marked activation of SAPK/JNK and NFκB, with slight or no effects on Akt, STAT-1/-3, ERK-1/2, and p38 MAPK, seemingly accounting for the better survival of M1 and TNFα secretion. In a microfluidically-supported human tumour biochip model, circulating ChA-treated M1 markedly reduced tumour cell viability through enhanced release of TNFα. Together, ChA may cause an anti-tumoural microenvironment by depletion of M2 and activation of M1, suggesting induction of G-actin nucleation as potential strategy to target tumour-associated macrophages in addition to neoplastic cells.en
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleModulation of actin dynamics as potential macrophage subtype-targeting anti-tumour strategy.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Institut für pharmazeutische Forschung Saarland, Universitätscampus E8.1, 66123 Saarbrücken, Germany.en
dc.identifier.journalScientific reportsen

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