355 Targeting the STAT6 pathway to inhibit tumor-associated macrophages-induced tumor growth and metastasis in breast cancer

Binnemars-Postma, Karin; Bansal, Ruchi; Storm, Gert; Prakash, J.

doi:10.1016/s0959-8049(16)30218-0

Cited by 2 publications

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“…To probe potential downstream mechanisms underlying Piezo1-mediated effects, we examined the role of Piezo1 in regulating transcription factors involved in macrophage activation. Nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) and signal transducer and activator of transcription 6 (STAT6) are essential transcription factors in inflammatory and healing activation, respectively [35][36][37][38][39][40][41][42] . In addition, the activation of both transcription factors is known to be dependent on Ca 2+ , where increased intracellular Ca 2+ has been shown to enhance NFκB and dampen STAT6 activation 25,43 .…”

Section: Resultsmentioning

confidence: 99%

“…We propose that soluble cues, such as IFNγ/LPS, may prime the channel's response to mechanical cues, thus regulating the downstream responses to mechanical signals in different contexts. It is possible that Ca 2+ signals could also arise by store operated Ca 2+ entry (SOCE) through Ca 2+ release-activated Ca 2+ (CRAC) channels, which regulate signaling pathways essential for T-cell activation 36 , though these channels have been shown to have a minimal role in many macrophage functions 37 . Our observations that Piezo1 potentiates NFκB and mitigates STAT6 is consistent with reports that show increased intracellular Ca 2 activates NFκB and suppresses STAT6 in immune cells through Ca 2+ -dependent molecules such as calpains 25,43 .…”

Section: Discussionmentioning

confidence: 99%

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Mechanically activated ion channel Piezo1 modulates macrophage polarization and stiffness sensing

et al. 2021

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Macrophages perform diverse functions within tissues during immune responses to pathogens and injury, but molecular mechanisms by which physical properties of the tissue regulate macrophage behavior are less well understood. Here, we examine the role of the mechanically activated cation channel Piezo1 in macrophage polarization and sensing of microenvironmental stiffness. We show that macrophages lacking Piezo1 exhibit reduced inflammation and enhanced wound healing responses. Additionally, macrophages expressing the transgenic Ca2+ reporter, Salsa6f, reveal that Ca2+ influx is dependent on Piezo1, modulated by soluble signals, and enhanced on stiff substrates. Furthermore, stiffness-dependent changes in macrophage function, both in vitro and in response to subcutaneous implantation of biomaterials in vivo, require Piezo1. Finally, we show that positive feedback between Piezo1 and actin drives macrophage activation. Together, our studies reveal that Piezo1 is a mechanosensor of stiffness in macrophages, and that its activity modulates polarization responses.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Mechanically activated ion channel Piezo1 modulates macrophage polarization and stiffness sensing

et al. 2021

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“…Tumor growth was significantly inhibited in the murine 4T1 mammary tumor model. Moreover, genetic markers for TAM infiltration (measured by F4/80 and YM-1 ) and pro-metastatic markers ( matrix metalloproteinase-2 ( MMP-2 ), Periostin and CD34 ) were significantly inhibited in the livers of treated mice, suggesting STAT6 is involved in the formation of the pre-metastatic niche [ 86 ].…”

Section: Targeting Strategies and Active Agentsmentioning

confidence: 99%

Nanomedicine Strategies to Target Tumor-Associated Macrophages

Binnemars-Postma

Storm

Prakash

2017

IJMS

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In recent years, the influence of the tumor microenvironment (TME) on cancer progression has been better understood. Macrophages, one of the most important cell types in the TME, exist in different subtypes, each of which has a different function. While classically activated M1 macrophages are involved in inflammatory and malignant processes, activated M2 macrophages are more involved in the wound-healing processes occurring in tumors. Tumor-associated macrophages (TAM) display M2 macrophage characteristics and support tumor growth and metastasis by matrix remodeling, neo-angiogenesis, and suppressing local immunity. Due to their detrimental role in tumor growth and metastasis, selective targeting of TAM for the treatment of cancer may prove to be beneficial in the treatment of cancer. Due to the plastic nature of macrophages, their activities may be altered to inhibit tumor growth. In this review, we will discuss the therapeutic options for the modulation and targeting of TAM. Different therapeutic strategies to deplete, inhibit recruitment of, or re-educate TAM will be discussed. Current strategies for the targeting of TAM using nanomedicine are reviewed. Passive targeting using different nanoparticle systems is described. Since TAM display a number of upregulated surface proteins compared to non-TAM, specific targeting using targeting ligands coupled to nanoparticles is discussed in detail.

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355 Targeting the STAT6 pathway to inhibit tumor-associated macrophages-induced tumor growth and metastasis in breast cancer

Cited by 2 publications

References 0 publications

Mechanically activated ion channel Piezo1 modulates macrophage polarization and stiffness sensing

Mechanically activated ion channel Piezo1 modulates macrophage polarization and stiffness sensing

Nanomedicine Strategies to Target Tumor-Associated Macrophages

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