Metastatic niche functions and therapeutic opportunities

Celià-Terrassa, Toni; Kang, Yibin

doi:10.1038/s41556-018-0145-9

Cited by 141 publications

(99 citation statements)

References 149 publications

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“…Metastatic niches create a permissive environment for metastasis formation. The main consequence of the interaction between metastasis‐initiating cells and the premetastatic niche is enhanced cancer stemness and plasticity, as well as metastasis‐favouring immune interplay and editing . TDEs contain various components, including microRNAs, and can regulate intercellular communication in premetastatic sites .…”

Section: Introductionmentioning

confidence: 99%

“…The main consequence of the interaction between metastasis-initiating cells and the premetastatic niche is enhanced cancer stemness and plasticity, as well as metastasis-favouring immune interplay and editing. 8 TDEs contain various components, including microRNAs, and can regulate intercellular communication in premetastatic sites. [9][10][11] MicroRNAs can be delivered into cells within microvesicles, apoptotic bodies, lipoproteins and ribonucleoproteins.…”

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confidence: 99%

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miR‐155 overexpression is followed by downregulation of its target gene, NFE2L2, and altered pattern of VEGFA expression in the liver of melanoma B16‐bearing mice at the premetastatic stage

Aksenenko

Palkina

Сергеева

et al. 2019

Int J Experimental Path

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Summary MicroRNAs are involved in the control of tumour progression and in metastatic cascade dynamics. However, the role of microRNAs in distant organ reorganization at the premetastatic stage is less clear, although the process of premetastatic niche formation is a crucial event according to modern concepts of tumour dissemination. The role of the present study was to investigate the expression levels of miR‐155, miR‐21, miR‐205 and miR‐let7b, as well as that of their target genes, in target organs of melanoma metastasis at the premetastatic stage. The expression levels of both the pro‐oncogenic miR‐155 and the tumour suppressive miR‐205 were found to be altered in the premetastatic liver of melanoma B16‐bearing mice. Bioinformatics analysis identified the target genes of miR‐155 to be nuclear factor, erythroid 2 like 2 (NFE2L2), secretogranin II, miR‐205, semaphorin 5A and vascular endothelial growth factor A (VEGFA). Among those, the redox status regulatory factor NFE2L2 was downregulated, which corresponded to increased levels of miR‐155. Due to the ability of pro‐oxidative events to initiate angiogenesis, VEGFA levels were evaluated in the premetastatic liver by immunohistochemistry, which revealed increased VEGFA expression in the central parts of the organ and diminished expression in the periphery. Taken together, these findings may support the concept of functional organ reorganization due to melanoma progression.

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Section: Introductionmentioning

confidence: 99%

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confidence: 99%

miR‐155 overexpression is followed by downregulation of its target gene, NFE2L2, and altered pattern of VEGFA expression in the liver of melanoma B16‐bearing mice at the premetastatic stage

Aksenenko

Palkina

Сергеева

et al. 2019

Int J Experimental Path

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“…Vascular leakage and infiltration of myeloid cells were important for the response to doxorubicin or cisplatin in breast carcinomas . These findings have underscored the importance of considering the role of the tumor microenvironment when designing chemotherapeutic strategies …”

Section: Translational Potential Of Iv‐mpm For Cancermentioning

confidence: 99%

“…33 These findings have underscored the importance of considering the role of the tumor microenvironment when designing chemotherapeutic strategies. 148 IV-MPM can be used to monitor therapy response and improve already effective therapies, such as immunotherapy. Adoptive cell therapy and cyclophosphamide (ACT-CTX) is one of the most effective treatments against melanoma.…”

Section: IVmentioning

confidence: 99%

Frontiers in intravital multiphoton microscopy of cancer

2019

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Background Cancer is a highly complex disease, which involves the cooperation of tumor cells with multiple types of host cells and the extracellular matrix. Cancer studies that rely solely on static measurements of individual cell types are insufficient to dissect this complexity. In the last two decades, intravital microscopy has established itself as a powerful technique that can significantly improve our understanding of cancer by revealing the dynamic interactions governing cancer initiation, progression, and treatment effects in living animals. This review focuses on intravital multiphoton microscopy (IV‐MPM) applications in mouse models of cancer. Recent findings IV‐MPM studies have already enabled a deeper understanding of the complex events occurring in cancer at the molecular, cellular, and tissue levels. Multiple cell types present in different tissues influence cancer cell behavior via activation of distinct signaling pathways. As a result, the boundaries in the field of IV‐MPM are continuously being pushed to provide an integrated comprehension of cancer. We propose that optics, informatics, and cancer (cell) biology are coevolving as a new field. We have identified four emerging themes in this new field. First, new microscopy systems and image processing algorithms are enabling the simultaneous identification of multiple interactions between the tumor cells and the components of the tumor microenvironment. Second, techniques from molecular biology are being exploited to visualize subcellular structures and protein activities within individual cells of interest and relate those to phenotypic decisions, opening the door for “in vivo cell biology”. Third, combining IV‐MPM with additional imaging modalities or omics studies holds promise for linking the cell phenotype to its genotype, metabolic state, or tissue location. Finally, the clinical use of IV‐MPM for analyzing efficacy of anticancer treatments is steadily growing, suggesting a future role of IV‐MPM for personalized medicine. Conclusion IV‐MPM has revolutionized visualization of tumor‐microenvironment interactions in real time. Moving forward, incorporation of novel optics, automated image processing, and omics technologies in the study of cancer biology, will not only advance our understanding of the underlying complexities but will also leverage the unique aspects of IV‐MPM for clinical use.

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“…Prior to the formation of overt metastatic disease, DTCs persist in the brain for months or years, and effective engagement with the metastatic niche is essential for colonization and outgrowth (Harper et al, 2016; Hosseini et al, 2016; Massagué and Obenauf, 2016; Sosa et al, 2014 . While the classic 'seed and soil' hypothesis highlights the importance of optimal DTCs arriving in a permissive metastatic microenvironment, recent studies into metastatic seeding, dormany, and outgrowth have revealed dynamic coevolutionary processes between DTCs and the metastatic niche (CeliàTerrassa and Kang, 2018) . Indeed, successful metastatic adaptation requires organspecific interactions with the surrounding parenchymal cells and extracellular matrix (Obenauf and Massagué, 2015) , and the diversity of these interactions (Chen et al, 2016; ContrerasZárate et al, 2019; Er et al, 2018; Schnepp et al, 2017; Zhang et al, 2015 , combined with the evolving heterogeneity of the DTCs themselves, renders the mechanistic dissection required for the development of treatment options challenging.…”

Section: Introductionmentioning

confidence: 99%

Rab11b-mediated integrin recycling promotes brain metastatic adaptation and outgrowth

Howe

Burnette

Justice

et al. 2019

Preprint

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Manuscript Summary:Rab11b upregulation in the brain microenvironment promotes recycling of cargo proteins required for breast cancer brain metastasis, including increased surface expression of integrin β1, which allows brain extracellular matrix attachment and mechanotransduction. Inhibition of the mevalonate pathway with statins prevents geranylgeranylation of Rab11b, decreasing cargo recycling, and inhibiting brain metastasis. Declaration of Conflict of Interest:The authors declare no competing interests. 6/10/2019Rab11b-mediated integrin recycling promotes brain metastatic adaptation and outgrowth -Google Docs https://docs.google.com/document/d/133ky5YwP8HxilKMV1nLO0styFXb_a77AufdN8Q_jytI/edit 2/27 GRAPHICAL ABSTRACT SUMMARYBreast cancer brain metastases (BCBM) have a 520 year latency and account for up to 30% of mortality.Developing new therapeutics requires a molecular understanding of adaptation to the brain microenvironment.Here, we combined RNAsequencing of BCBM development with a reverse genetic screen in Drosophila melanogaster and identified Rab11b, an endosomal recycling protein, as a mediator of metastatic adaptation.We show that disseminated cells upregulate Rab11b early after arrival in the brain, allowing control of the cell surface proteome through recycling of proteins required for successful interaction with the microenvironment, including integrin β1. Rab11bmediated control of integrin β1 surface expression allows ligation to the brain ECM, activating mechanotransduction signaling to allow survival and proliferation. We propose a model in which upregulation of Rab11b allows disseminated cells to recycle needed proteins during metastatic adaptation, without strictly requiring transcription and translation, to allow for metastatic outgrowth. 6/10/2019 Rab11b-mediated integrin recycling promotes brain metastatic adaptation and outgrowth -Google Docs https://docs.google.com/document/d/133ky5YwP8HxilKMV1nLO0styFXb_a77AufdN8Q_jytI/edit 3/27 AUTHOR

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Metastatic niche functions and therapeutic opportunities

Cited by 141 publications

References 149 publications

miR‐155 overexpression is followed by downregulation of its target gene, NFE2L2, and altered pattern of VEGFA expression in the liver of melanoma B16‐bearing mice at the premetastatic stage

miR‐155 overexpression is followed by downregulation of its target gene, NFE2L2, and altered pattern of VEGFA expression in the liver of melanoma B16‐bearing mice at the premetastatic stage

Frontiers in intravital multiphoton microscopy of cancer

Rab11b-mediated integrin recycling promotes brain metastatic adaptation and outgrowth

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