In vivo morphological alterations of TAMs during KCa3.1 inhibition—by using in vivo two-photon time-lapse technology

Tumor associated macrophages (TAMs) are the mostprevalent cells recruited in the tumor microenvironment (TME). Once recruited, TAMs acquire a pro-tumor phenotype characterized by a typical morphology: ameboid in the tumor core and with larger soma and thick branches in the tumor periphery. Targeting...
Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Francesca Massenzio [verfasserIn] Marco Cambiaghi [verfasserIn] Federica Marchiotto [verfasserIn] Diana Boriero [verfasserIn] Cristina Limatola [verfasserIn] Giuseppina D’Alessandro [verfasserIn] Mario Buffelli [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	Ca2+ activated K+ channels TRAM-34 tumor associated macrophages (TAMs) immune cells in the glioma two-photon imaging

Übergeordnetes Werk:	In: Frontiers in Cellular Neuroscience - Frontiers Media S.A., 2008, 16(2022)
Übergeordnetes Werk:	volume:16 ; year:2022

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fncel.2022.1002487

Katalog-ID:	DOAJ002223023

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allfieldsGer	10.3389/fncel.2022.1002487 doi (DE-627)DOAJ002223023 (DE-599)DOAJ8418faa956394237a2923feb2680addf DE-627 ger DE-627 rakwb eng RC321-571 Francesca Massenzio verfasserin aut In vivo morphological alterations of TAMs during KCa3.1 inhibition—by using in vivo two-photon time-lapse technology 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Tumor associated macrophages (TAMs) are the mostprevalent cells recruited in the tumor microenvironment (TME). Once recruited, TAMs acquire a pro-tumor phenotype characterized by a typical morphology: ameboid in the tumor core and with larger soma and thick branches in the tumor periphery. Targeting TAMs by reverting them to an anti-tumor phenotype is a promising strategy for cancer immunotherapy. Taking advantage of Cx3cr1GFP/WT heterozygous mice implanted with murine glioma GL261-RFP cells we investigated the role of Ca2+-activated K+ channel (KCa3.1) on the phenotypic shift of TAMs at the late stage of glioma growth through in vivo two-photon imaging. We demonstrated that TAMs respond promptly to KCa3.1 inhibition using a selective inhibitor of the channel (TRAM-34) in a time-dependent manner by boosting ramified projections attributable to a less hypertrophic phenotype in the tumor core. We also revealed a selective effect of drug treatment by reducing both glioma cells and TAMs in the tumor core with no interference with surrounding cells. Taken together, our data indicate a TRAM-34-dependent progressive morphological transformation of TAMs toward a ramified and anti-tumor phenotype, suggesting that the timing of KCa3.1 inhibition is a key point to allow beneficial effects on TAMs. Ca2+ activated K+ channels TRAM-34 tumor associated macrophages (TAMs) immune cells in the glioma two-photon imaging Neurosciences. Biological psychiatry. Neuropsychiatry Marco Cambiaghi verfasserin aut Federica Marchiotto verfasserin aut Diana Boriero verfasserin aut Cristina Limatola verfasserin aut Cristina Limatola verfasserin aut Giuseppina D’Alessandro verfasserin aut Giuseppina D’Alessandro verfasserin aut Mario Buffelli verfasserin aut In Frontiers in Cellular Neuroscience Frontiers Media S.A., 2008 16(2022) (DE-627)579826414 (DE-600)2452963-1 16625102 nnns volume:16 year:2022 https://doi.org/10.3389/fncel.2022.1002487 kostenfrei https://doaj.org/article/8418faa956394237a2923feb2680addf kostenfrei https://www.frontiersin.org/articles/10.3389/fncel.2022.1002487/full kostenfrei https://doaj.org/toc/1662-5102 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 16 2022
allfieldsSound	10.3389/fncel.2022.1002487 doi (DE-627)DOAJ002223023 (DE-599)DOAJ8418faa956394237a2923feb2680addf DE-627 ger DE-627 rakwb eng RC321-571 Francesca Massenzio verfasserin aut In vivo morphological alterations of TAMs during KCa3.1 inhibition—by using in vivo two-photon time-lapse technology 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Tumor associated macrophages (TAMs) are the mostprevalent cells recruited in the tumor microenvironment (TME). Once recruited, TAMs acquire a pro-tumor phenotype characterized by a typical morphology: ameboid in the tumor core and with larger soma and thick branches in the tumor periphery. Targeting TAMs by reverting them to an anti-tumor phenotype is a promising strategy for cancer immunotherapy. Taking advantage of Cx3cr1GFP/WT heterozygous mice implanted with murine glioma GL261-RFP cells we investigated the role of Ca2+-activated K+ channel (KCa3.1) on the phenotypic shift of TAMs at the late stage of glioma growth through in vivo two-photon imaging. We demonstrated that TAMs respond promptly to KCa3.1 inhibition using a selective inhibitor of the channel (TRAM-34) in a time-dependent manner by boosting ramified projections attributable to a less hypertrophic phenotype in the tumor core. We also revealed a selective effect of drug treatment by reducing both glioma cells and TAMs in the tumor core with no interference with surrounding cells. Taken together, our data indicate a TRAM-34-dependent progressive morphological transformation of TAMs toward a ramified and anti-tumor phenotype, suggesting that the timing of KCa3.1 inhibition is a key point to allow beneficial effects on TAMs. Ca2+ activated K+ channels TRAM-34 tumor associated macrophages (TAMs) immune cells in the glioma two-photon imaging Neurosciences. Biological psychiatry. Neuropsychiatry Marco Cambiaghi verfasserin aut Federica Marchiotto verfasserin aut Diana Boriero verfasserin aut Cristina Limatola verfasserin aut Cristina Limatola verfasserin aut Giuseppina D’Alessandro verfasserin aut Giuseppina D’Alessandro verfasserin aut Mario Buffelli verfasserin aut In Frontiers in Cellular Neuroscience Frontiers Media S.A., 2008 16(2022) (DE-627)579826414 (DE-600)2452963-1 16625102 nnns volume:16 year:2022 https://doi.org/10.3389/fncel.2022.1002487 kostenfrei https://doaj.org/article/8418faa956394237a2923feb2680addf kostenfrei https://www.frontiersin.org/articles/10.3389/fncel.2022.1002487/full kostenfrei https://doaj.org/toc/1662-5102 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 16 2022
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callnumber-first	R - Medicine
author	Francesca Massenzio
spellingShingle	Francesca Massenzio misc RC321-571 misc Ca2+ activated K+ channels misc TRAM-34 misc tumor associated macrophages (TAMs) misc immune cells in the glioma misc two-photon imaging misc Neurosciences. Biological psychiatry. Neuropsychiatry In vivo morphological alterations of TAMs during KCa3.1 inhibition—by using in vivo two-photon time-lapse technology
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topic_title	RC321-571 In vivo morphological alterations of TAMs during KCa3.1 inhibition—by using in vivo two-photon time-lapse technology Ca2+ activated K+ channels TRAM-34 tumor associated macrophages (TAMs) immune cells in the glioma two-photon imaging
topic	misc RC321-571 misc Ca2+ activated K+ channels misc TRAM-34 misc tumor associated macrophages (TAMs) misc immune cells in the glioma misc two-photon imaging misc Neurosciences. Biological psychiatry. Neuropsychiatry
topic_unstemmed	misc RC321-571 misc Ca2+ activated K+ channels misc TRAM-34 misc tumor associated macrophages (TAMs) misc immune cells in the glioma misc two-photon imaging misc Neurosciences. Biological psychiatry. Neuropsychiatry
topic_browse	misc RC321-571 misc Ca2+ activated K+ channels misc TRAM-34 misc tumor associated macrophages (TAMs) misc immune cells in the glioma misc two-photon imaging misc Neurosciences. Biological psychiatry. Neuropsychiatry
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title	In vivo morphological alterations of TAMs during KCa3.1 inhibition—by using in vivo two-photon time-lapse technology
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title_full	In vivo morphological alterations of TAMs during KCa3.1 inhibition—by using in vivo two-photon time-lapse technology
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author_browse	Francesca Massenzio Marco Cambiaghi Federica Marchiotto Diana Boriero Cristina Limatola Giuseppina D’Alessandro Mario Buffelli
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title_sort	in vivo morphological alterations of tams during kca3.1 inhibition—by using in vivo two-photon time-lapse technology
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title_auth	In vivo morphological alterations of TAMs during KCa3.1 inhibition—by using in vivo two-photon time-lapse technology
abstract	Tumor associated macrophages (TAMs) are the mostprevalent cells recruited in the tumor microenvironment (TME). Once recruited, TAMs acquire a pro-tumor phenotype characterized by a typical morphology: ameboid in the tumor core and with larger soma and thick branches in the tumor periphery. Targeting TAMs by reverting them to an anti-tumor phenotype is a promising strategy for cancer immunotherapy. Taking advantage of Cx3cr1GFP/WT heterozygous mice implanted with murine glioma GL261-RFP cells we investigated the role of Ca2+-activated K+ channel (KCa3.1) on the phenotypic shift of TAMs at the late stage of glioma growth through in vivo two-photon imaging. We demonstrated that TAMs respond promptly to KCa3.1 inhibition using a selective inhibitor of the channel (TRAM-34) in a time-dependent manner by boosting ramified projections attributable to a less hypertrophic phenotype in the tumor core. We also revealed a selective effect of drug treatment by reducing both glioma cells and TAMs in the tumor core with no interference with surrounding cells. Taken together, our data indicate a TRAM-34-dependent progressive morphological transformation of TAMs toward a ramified and anti-tumor phenotype, suggesting that the timing of KCa3.1 inhibition is a key point to allow beneficial effects on TAMs.
abstractGer	Tumor associated macrophages (TAMs) are the mostprevalent cells recruited in the tumor microenvironment (TME). Once recruited, TAMs acquire a pro-tumor phenotype characterized by a typical morphology: ameboid in the tumor core and with larger soma and thick branches in the tumor periphery. Targeting TAMs by reverting them to an anti-tumor phenotype is a promising strategy for cancer immunotherapy. Taking advantage of Cx3cr1GFP/WT heterozygous mice implanted with murine glioma GL261-RFP cells we investigated the role of Ca2+-activated K+ channel (KCa3.1) on the phenotypic shift of TAMs at the late stage of glioma growth through in vivo two-photon imaging. We demonstrated that TAMs respond promptly to KCa3.1 inhibition using a selective inhibitor of the channel (TRAM-34) in a time-dependent manner by boosting ramified projections attributable to a less hypertrophic phenotype in the tumor core. We also revealed a selective effect of drug treatment by reducing both glioma cells and TAMs in the tumor core with no interference with surrounding cells. Taken together, our data indicate a TRAM-34-dependent progressive morphological transformation of TAMs toward a ramified and anti-tumor phenotype, suggesting that the timing of KCa3.1 inhibition is a key point to allow beneficial effects on TAMs.
abstract_unstemmed	Tumor associated macrophages (TAMs) are the mostprevalent cells recruited in the tumor microenvironment (TME). Once recruited, TAMs acquire a pro-tumor phenotype characterized by a typical morphology: ameboid in the tumor core and with larger soma and thick branches in the tumor periphery. Targeting TAMs by reverting them to an anti-tumor phenotype is a promising strategy for cancer immunotherapy. Taking advantage of Cx3cr1GFP/WT heterozygous mice implanted with murine glioma GL261-RFP cells we investigated the role of Ca2+-activated K+ channel (KCa3.1) on the phenotypic shift of TAMs at the late stage of glioma growth through in vivo two-photon imaging. We demonstrated that TAMs respond promptly to KCa3.1 inhibition using a selective inhibitor of the channel (TRAM-34) in a time-dependent manner by boosting ramified projections attributable to a less hypertrophic phenotype in the tumor core. We also revealed a selective effect of drug treatment by reducing both glioma cells and TAMs in the tumor core with no interference with surrounding cells. Taken together, our data indicate a TRAM-34-dependent progressive morphological transformation of TAMs toward a ramified and anti-tumor phenotype, suggesting that the timing of KCa3.1 inhibition is a key point to allow beneficial effects on TAMs.
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title_short	In vivo morphological alterations of TAMs during KCa3.1 inhibition—by using in vivo two-photon time-lapse technology
url	https://doi.org/10.3389/fncel.2022.1002487 https://doaj.org/article/8418faa956394237a2923feb2680addf https://www.frontiersin.org/articles/10.3389/fncel.2022.1002487/full https://doaj.org/toc/1662-5102
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In vivo morphological alterations of TAMs during KCa3.1 inhibition—by using in vivo two-photon time-lapse technology

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