Targeting signalling pathways and the immune microenvironment of cancer stem cells — a clinical update

Clara, Joseph A.; Monge, Cecilia; Yang, Yingzi; Takebe, Naoko

doi:10.1038/s41571-019-0293-2

Cited by 540 publications

(476 citation statements)

References 248 publications

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“…Notch signaling is a fundamental player in the establishment of stem cell fate and behavior in development, regeneration and disease [12][13][14]49]. Notch signaling was shown to be necessary for the maintenance of cancer stem cells in different types of tumors [18,[50][51][52]. As such, it is the target of numerous therapeutic antineoplastic approaches [15,18,53].…”

Section: Discussionmentioning

confidence: 99%

Ameloblastomas Exhibit Stem Cell Potential, Possess Neurotrophic Properties, and Establish Connections with Trigeminal Neurons

Pagella

Catón

Meisel

et al. 2020

Cells

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Ameloblastomas are locally invasive and aggressive odontogenic tumors treated via surgical resection, which results in facial deformity and significant morbidity. Few studies have addressed the cellular and molecular events of ameloblastoma onset and progression, thus hampering the development of non-invasive therapeutic approaches. Tumorigenesis is driven by a plethora of factors, among which innervation has been long neglected. Recent findings have shown that innervation directly promotes tumor progression. On this basis, we investigated the molecular characteristics and neurotrophic properties of human ameloblastomas. Our results showed that ameloblastomas express dental epithelial stem cell markers, as well as components of the Notch signaling pathway, indicating persistence of stemness. We demonstrated that ameloblastomas express classical stem cell markers, exhibit stem cell potential, and form spheres. These tumors express also molecules of the Notch signaling pathway, fundamental for stem cells and their fate. Additionally, we showed that ameloblastomas express the neurotrophic factors NGF and BDNF, as well as their receptors TRKA, TRKB, and P75/NGFR, which are responsible for their innervation by trigeminal axons in vivo. In vitro studies using microfluidic devices showed that ameloblastoma cells attract and form connections with these nerves. Innervation of ameloblastomas might play a key role in the onset of this malignancy and might represent a promising target for non-invasive pharmacological interventions.

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Section: Discussionmentioning

confidence: 99%

Ameloblastomas Exhibit Stem Cell Potential, Possess Neurotrophic Properties, and Establish Connections with Trigeminal Neurons

Pagella

Catón

Meisel

et al. 2020

Cells

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“…Clinically, less neointima in moderate alcohol consumers would conceivably translate to reduced heart attacks and strokes. Of note, Sonic Hedgehog signaling has previously been implicated in the pathogenesis of vessel disease (Aravani et al, 2019) (Morrow et al, 2007) (Morrow et al, 2009 (Li et al, 2012;Passman et al, 2008;Walshe et al, 2011) as well as in the regulation of stem cell fate especially in different cancers (Clara et al, 2020;Sharma et al, 2019;Tandon et al, 2019). Moreover, several studies have implicated Sonic Hedgehog signaling as an important molecular target for alcohol during development (Ahlgren et al, 2002) and in adult tissues (Latchoumycandane et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Moderate Alcohol Consumption Targets S100β⁺ Vascular Stem Cells and Attenuates Injury‐Induced Neointimal Hyperplasia

Liu

Harman

DiLuca

et al. 2020

Alcoholism Clin & Exp Res

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Background Stem cells present in the vessel wall may be triggered in response to injurious stimuli to undergo differentiation and contribute to vascular disease development. Our aim was to determine the effect of moderate alcohol (EtOH) exposure on the expansion and differentiation of S100 calcium‐binding protein B positive (S100β+) resident vascular stem cells and their contribution to pathologic vessel remodeling in a mouse model of arteriosclerosis. Methods and Results Lineage tracing analysis of S100β+ cells was performed in male and female S100β‐eGFP/Cre/ERT2–dTomato transgenic mice treated daily with or without EtOH by oral gavage (peak BAC: 15 mM or 0.07%) following left common carotid artery ligation for 14 days. Carotid arteries (ligated or sham‐operated) were harvested for morphological analysis and confocal assessment of fluorescent‐tagged S100 β + cells in FFPE carotid cross sections. Ligation‐induced carotid remodeling was more robust in males than in females. EtOH‐gavaged mice had less adventitial thickening and markedly reduced neointimal formation compared to controls, with a more pronounced inhibitory effect in males compared to females. There was significant expansion of S100β+‐marked cells in vessels postligation, primarily in the neointimal compartment. EtOH treatment reduced the fraction of S100β+ cells in carotid cross sections, concomitant with attenuated remodeling. In vitro, EtOH attenuated Sonic Hedgehog‐stimulated myogenic differentiation (as evidenced by reduced calponin and myosin heavy chain expression) of isolated murine S100β+ vascular stem cells. Conclusions These data highlight resident vascular S100β+ stem cells as a novel target population for alcohol and suggest that regulation of these progenitors in adult arteries, particularly in males, may be an important mechanism contributing to the antiatherogenic effects of moderate alcohol consumption.

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“…Important insights arise from the role of some PRDMs in the control of Wnt/β-catenin and Notch pathways. It is extensively reported that Wnt and Notch signaling are widely associated with chemoresistance and cancer stem cells control, in different tumors, including colon, breast, pancreatic cancers, and gliomas [296]. In recent years, the need of an effective strategy to eradicate cancer stem cells, considering the tumor fuel, has become evident.…”

Section: Clinical Value Of Prdms In Cancer and Concluding Remarksmentioning

confidence: 99%

Multifaceted Role of PRDM Proteins in Human Cancer

Casamassimi

Rienzo

Zazzo

et al. 2020

IJMS

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The PR/SET domain family (PRDM) comprise a family of genes whose protein products share a conserved N-terminal PR [PRDI-BF1 (positive regulatory domain I-binding factor 1) and RIZ1 (retinoblastoma protein-interacting zinc finger gene 1)] homologous domain structurally and functionally similar to the catalytic SET [Su(var)3-9, enhancer-of-zeste and trithorax] domain of histone methyltransferases (HMTs). These genes are involved in epigenetic regulation of gene expression through their intrinsic HMTase activity or via interactions with other chromatin modifying enzymes. In this way they control a broad spectrum of biological processes, including proliferation and differentiation control, cell cycle progression, and maintenance of immune cell homeostasis. In cancer, tumor-specific dysfunctions of PRDM genes alter their expression by genetic and/or epigenetic modifications. A common characteristic of most PRDM genes is to encode for two main molecular variants with or without the PR domain. They are generated by either alternative splicing or alternative use of different promoters and play opposite roles, particularly in cancer where their imbalance can be often observed. In this scenario, PRDM proteins are involved in cancer onset, invasion, and metastasis and their altered expression is related to poor prognosis and clinical outcome. These functions strongly suggest their potential use in cancer management as diagnostic or prognostic tools and as new targets of therapeutic intervention.

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Targeting signalling pathways and the immune microenvironment of cancer stem cells — a clinical update

Cited by 540 publications

References 248 publications

Ameloblastomas Exhibit Stem Cell Potential, Possess Neurotrophic Properties, and Establish Connections with Trigeminal Neurons

Ameloblastomas Exhibit Stem Cell Potential, Possess Neurotrophic Properties, and Establish Connections with Trigeminal Neurons

Moderate Alcohol Consumption Targets S100β⁺ Vascular Stem Cells and Attenuates Injury‐Induced Neointimal Hyperplasia

Multifaceted Role of PRDM Proteins in Human Cancer

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Targeting signalling pathways and the immune microenvironment of cancer stem cells — a clinical update

Cited by 540 publications

References 248 publications

Ameloblastomas Exhibit Stem Cell Potential, Possess Neurotrophic Properties, and Establish Connections with Trigeminal Neurons

Ameloblastomas Exhibit Stem Cell Potential, Possess Neurotrophic Properties, and Establish Connections with Trigeminal Neurons

Moderate Alcohol Consumption Targets S100β+ Vascular Stem Cells and Attenuates Injury‐Induced Neointimal Hyperplasia

Multifaceted Role of PRDM Proteins in Human Cancer

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Resources

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Moderate Alcohol Consumption Targets S100β⁺ Vascular Stem Cells and Attenuates Injury‐Induced Neointimal Hyperplasia