The soluble glycoprotein NMB (GPNMB) produced by macrophages induces cancer stemness and metastasis via CD44 and IL-33

Liguori, Manuela; Digifico, Elisabeth; Vacchini, Alessandro; Avigni, Roberta; Colombo, Federico; Borroni, Elena Monica; Farina, Francesca; Milanesi, Samantha; Castagna, Alessandra; Mannarino, Laura; Craparotta, Ilaria; Marchini, Sergio; Erba, Eugenio; Panini, Nicolò; Tamborini, Matteo; Rimoldi, Valeria; Allavena, Paola; Belgiovine, Cristina

doi:10.1038/s41423-020-0501-0

Cited by 64 publications

(56 citation statements)

References 70 publications

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“…In tumors, also the CSCs reside in a cancer niche that defends them from stress signals, such as apoptosis-inducing chemotherapeutic agents and from attacks by the immune system (Hanahan and Coussens 2012 ; Hsu and Fuchs 2012 ; Korkaya et al 2011 ; Plaks et al 2015 ). As detailed below, key players in the cancer niche are TAMs, which indeed secrete a variety of soluble factors and physically interact with CSCs to protect them from environmental damage (Fan et al 2014 ; Jinushi et al 2011 ; Liguori et al 2021 ; Lu et al 2014 ; Zhou et al 2015 ; Oshimori 2020 ; Raghavan et al 2019 ).…”

Section: Main Textmentioning

confidence: 99%

“…Among immune cells producing GPNMB are macrophages and dendritic cells (Solinas et al 2010 ; Chung et al 2020 ; Yu et al 2016 ). Our group reported that GPNMB is actively transcribed when macrophages are co-cultured with cancer cells (Solinas et al 2010 ); furthermore, it is preferentially expressed by M2 macrophages (Liguori et al 2021 ; Yu et al 2016 ) and TAMs in mouse experimental tumors are positive for GPNMB (Liguori et al 2021 ).…”

Section: Main Textmentioning

confidence: 99%

“…CD199 and CD117 and Sca-1), as well as genes coding for stem cell transcription factors (e.g. Nanog , Oct3/4 , DNMT and Brachyury ) (Liguori et al 2021 ). Similar results were demonstrated in GPNMB-transduced tumor cells that showed a remarkably high tumorigenicity and metastatic ability in vivo (Liguori et al 2021 ).…”

Section: Main Textmentioning

confidence: 99%

“…CSCs can be defined in vitro in functional assays (i.e., tumor-sphere assay), as cells with intrinsic drug resistance and self-renewal potential but are most commonly defined by the expression of stemness-related markers. CSCs-associated markers include: aldehyde dehydrogenase 1 (ALDH1), involved in intracellular retinoic acid production; ATP-binding cassette sub-family G member 2 (ABCG2); other surface markers such as CD133, CD44, CD24, CD34, CD90, CD117 and CD166 (Fan et al 2014 ; Jinushi et al 2011 ; Kreso and Dick 2014 ; Hermann et al 2007 ; Ginestier et al 2007 ; Medema 2013 ; Hanahan and Coussens 2012 ; Hsu and Fuchs 2012 ; Korkaya et al 2011 ; Liguori et al 2021 ; Lu et al 2014 ; Plaks et al 2015 ; Zhou et al 2015 ).…”

Section: Introductionmentioning

confidence: 99%

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Macrophages and cancer stem cells: a malevolent alliance

Allavena

Digifico

Belgiovine

2021

Mol Med

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Myeloid cells infiltrating tumors are gaining ever growing attention in the last years because their pro-tumor and immunosuppressive functions are relevant for disease progression and therapeutic responses. The functional ambiguity of tumor-associated macrophages (TAMs), mostly promoting tumor evolution, is a challenging hurdle. This is even more evident in the case of cancer stem cells (CSCs); as active participants in the specialized environment of the cancer stem cell niche, TAMs initiate a reciprocal conversation with CSCs. TAMs contribute to protect CSCs from the hostile environment (exogenous insults, toxic compounds, attacks from the immune cells), and produce several biologically active mediators that modulate crucial developmental pathways that sustain cancer cell stemness. In this review, we have focused our attention on the interaction between TAMs and CSCs; we describe how TAMs impact on CSC biology and, in turn, how CSCs exploit the tissue trophic activity of macrophages to survive and progress. Since CSCs are responsible for therapy resistance and tumor recurrence, they are important therapeutic targets. In view of the recent success in oncology obtained by stimulating the immune system, we discuss some macrophage-targeted therapeutic strategies that may also affect the CSCs and interrupt their malevolent alliance.

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Section: Main Textmentioning

confidence: 99%

Section: Main Textmentioning

confidence: 99%

Section: Main Textmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Macrophages and cancer stem cells: a malevolent alliance

Allavena

Digifico

Belgiovine

2021

Mol Med

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“…A TAM signature expressing SLC40A1, which encodes for the iron exporter ferroportin, and GPNMB, which encodes the glycoprotein nonmetastatic melanoma protein B (NMB), was correlated with poor prognosis in hepatocellular carcinoma [212]. The iron transporter has been previously associated with an attenuation of macrophage-mediated immunity [213] and the glycoprotein NMB was found to be upregulated by TAM and induce cancer stem cell markers and tumour progression via binding to the CD44 in tumour cells, eliciting the expression of IL-33 and its receptor in different murine cancer models [214].…”

Section: Macrophagesmentioning

confidence: 99%

3D Cancer Models: Depicting Cellular Crosstalk within the Tumour Microenvironment

Franchi-Mendes

Eduardo

Domenici

et al. 2021

Cancers

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The tumour microenvironment plays a critical role in tumour progression and drug resistance processes. Non-malignant cell players, such as fibroblasts, endothelial cells, immune cells and others, interact with each other and with the tumour cells, shaping the disease. Though the role of each cell type and cell communication mechanisms have been progressively studied, the complexity of this cellular network and its role in disease mechanism and therapeutic response are still being unveiled. Animal models have been mainly used, as they can represent systemic interactions and conditions, though they face recognized limitations in translational potential due to interspecies differences. In vitro 3D cancer models can surpass these limitations, by incorporating human cells, including patient-derived ones, and allowing a range of experimental designs with precise control of each tumour microenvironment element. We summarize the role of each tumour microenvironment component and review studies proposing 3D co-culture strategies of tumour cells and non-malignant cell components. Moreover, we discuss the potential of these modelling approaches to uncover potential therapeutic targets in the tumour microenvironment and assess therapeutic efficacy, current bottlenecks and perspectives.

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Pan‐Cancer Single‐Nucleus Total RNA Sequencing Using snHH‐Seq

Chen,

Fang,

Shao

et al. 2023

Advanced Science

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Tumor heterogeneity and its drivers impair tumor progression and cancer therapy. Single‐cell RNA sequencing is used to investigate the heterogeneity of tumor ecosystems. However, most methods of scRNA‐seq amplify the termini of polyadenylated transcripts, making it challenging to perform total RNA analysis and somatic mutation analysis.Therefore, a high‐throughput and high‐sensitivity method called snHH‐seq is developed, which combines random primers and a preindex strategy in the droplet microfluidic platform. This innovative method allows for the detection of total RNA in single nuclei from clinically frozen samples. A robust pipeline to facilitate the analysis of full‐length RNA‐seq data is also established. snHH‐seq is applied to more than 730 000 single nuclei from 32 patients with various tumor types. The pan‐cancer study enables it to comprehensively profile data on the tumor transcriptome, including expression levels, mutations, splicing patterns, clone dynamics, etc. New malignant cell subclusters and exploring their specific function across cancers are identified. Furthermore, the malignant status of epithelial cells is investigated among different cancer types with respect to mutation and splicing patterns. The ability to detect full‐length RNA at the single‐nucleus level provides a powerful tool for studying complex biological systems and has broad implications for understanding tumor pathology.

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The soluble glycoprotein NMB (GPNMB) produced by macrophages induces cancer stemness and metastasis via CD44 and IL-33

Cited by 64 publications

References 70 publications

Macrophages and cancer stem cells: a malevolent alliance

Macrophages and cancer stem cells: a malevolent alliance

3D Cancer Models: Depicting Cellular Crosstalk within the Tumour Microenvironment

Pan‐Cancer Single‐Nucleus Total RNA Sequencing Using snHH‐Seq

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