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

Massenzio, Francesca and Cambiaghi, Marco and Marchiotto, Federica and Boriero, Diana and Limatola, Cristina and D’Alessandro, Giuseppina and Buffelli, Mario (2022) In vivo morphological alterations of TAMs during KCa3.1 inhibition—by using in vivo two-photon time-lapse technology. Frontiers in Cellular Neuroscience, 16. ISSN 1662-5102

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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.

Item Type: Article
Subjects: West Bengal Archive > Medical Science
Depositing User: Unnamed user with email support@westbengalarchive.com
Date Deposited: 23 Mar 2023 07:14
Last Modified: 01 Aug 2024 09:32
URI: http://article.stmacademicwriting.com/id/eprint/338

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