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Modulation of actin dynamics as potential macrophage subtype-targeting anti-tumour strategy.

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)? 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 NF?B, 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 TNF? secretion. In a microfluidically-supported human tumour biochip model, circulating ChA-treated M1 markedly reduced tumour cell viability through enhanced release of TNF?. 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.

SUBMITTER: Pergola C

PROVIDER: S-EPMC5278352 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Modulation of actin dynamics as potential macrophage subtype-targeting anti-tumour strategy.

Pergola Carlo C Schubert Katrin K Pace Simona S Ziereisen Jana J Nikels Felix F Scherer Olga O Hüttel Stephan S Zahler Stefan S Vollmar Angelika M AM Weinigel Christina C Rummler Silke S Müller Rolf R Raasch Martin M Mosig Alexander A Koeberle Andreas A Werz Oliver O

Scientific reports 20170130

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. ...[more]

PMID: 28134280

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Dataset Information

Modulation of actin dynamics as potential macrophage subtype-targeting anti-tumour strategy.

Publications

Modulation of actin dynamics as potential macrophage subtype-targeting anti-tumour strategy.

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