Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
9.9
5.1
Journals
Cells
Special Issues
Human Cancer Modeling in Zebrafish to Improve Our Understanding and...
share announcement

Human Cancer Modeling in Zebrafish to Improve Our Understanding and Treatment

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: closed (15 February 2023) | Viewed by 38257

Special Issue Editor

Prof. Bogusława Ewa Snaar-Jagalska

E-Mail Website
Guest Editor
Gorlaeus Laboratories, Institute of Biology, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands

Special Issue Information

Dear Colleagues,

In this Special Issue of Cells, we invite your contributions, either in the form of original research articles, reviews, or shorter perspective articles on all aspects related to the theme of “Human Cancer Modeling in Zebrafish to Improve Our Understanding and Treatment”. Articles with molecular biological insight and translational perspective to clinic are especially welcome.

Relevant topics include but are not limited to:

  • Zebrafish as a model organism in cancer research;
  • Genetically induced cancer models;
  • Allo-, xeno-, ortotopic transplantation models;
  • Zebrafish avatars of human cancer;
  • Tumor microenvironment interactions;
  • Drug discovery and toxicity;
  • Compound administration and compound pharmacokinetics;
  • Cancer prevention.

Prof. Bogusława Ewa Snaar-Jagalska
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Zebrafish cancer models
  • ZF-avatars
  • Drug discovery
  • Drug administration
  • Cancer prevention

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue polices can be found here.

Published Papers (7 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

16 pages, 2310 KiB  
Article
Pharmacometabolic Effects of Pteryxin and Valproate on Pentylenetetrazole-Induced Seizures in Zebrafish Reveal Vagus Nerve Stimulation
by Adrianna Skiba, Daniele Pellegata, Veronika Morozova, Ewelina Kozioł, Barbara Budzyńska, Simon Ming-Yuen Lee, Jürg Gertsch and Krystyna Skalicka-Woźniak
Cells 2023, 12(11), 1540; https://doi.org/10.3390/cells12111540 - 4 Jun 2023
Cited by 4 | Viewed by 2450
Abstract
Zebrafish (Danio rerio) assays provide a versatile pharmacological platform to test compounds on a wide range of behaviors in a whole organism. A major challenge lies in the lack of knowledge about the bioavailability and pharmacodynamic effects of bioactive compounds in this model [...] Read more.
Zebrafish (Danio rerio) assays provide a versatile pharmacological platform to test compounds on a wide range of behaviors in a whole organism. A major challenge lies in the lack of knowledge about the bioavailability and pharmacodynamic effects of bioactive compounds in this model organism. Here, we employed a combined methodology of LC-ESI-MS/MS analytics and targeted metabolomics with behavioral experiments to evaluate the anticonvulsant and potentially toxic effects of the angular dihydropyranocoumarin pteryxin (PTX) in comparison to the antiepileptic drug sodium valproate (VPN) in zebrafish larvae. PTX occurs in different Apiaceae plants traditionally used in Europe to treat epilepsy but has not been investigated so far. To compare potency and efficacy, the uptake of PTX and VPN into zebrafish larvae was quantified as larvae whole-body concentrations together with amino acids and neurotransmitters as proxy pharmacodynamic readout. The convulsant agent pentylenetetrazole (PTZ) acutely reduced the levels of most metabolites, including acetylcholine and serotonin. Conversely, PTX strongly reduced neutral essential amino acids in a LAT1 (SLCA5)-independent manner, but, similarly to VPN specifically increased the levels of serotonin, acetylcholine, and choline, but also ethanolamine. PTX dose and time-dependent manner inhibited PTZ-induced seizure-like movements resulting in a ~70% efficacy after 1 h at 20 µM (the equivalent of 4.28 ± 0.28 µg/g in larvae whole-body). VPN treated for 1 h with 5 mM (the equivalent of 18.17 ± 0.40 µg/g in larvae whole-body) showed a ~80% efficacy. Unexpectedly, PTX (1–20 µM) showed significantly higher bioavailability than VPN (0.1–5 mM) in immersed zebrafish larvae, possibly because VPN in the medium dissociated partially to the readily bioavailable valproic acid. The anticonvulsive effect of PTX was confirmed by local field potential (LFP) recordings. Noteworthy, both substances specifically increased and restored whole-body acetylcholine, choline, and serotonin levels in control and PTZ-treated zebrafish larvae, indicative of vagus nerve stimulation (VNS), which is an adjunctive therapeutic strategy to treat refractory epilepsy in humans. Our study demonstrates the utility of targeted metabolomics in zebrafish assays and shows that VPN and PTX pharmacologically act on the autonomous nervous system by activating parasympathetic neurotransmitters. Full article
(This article belongs to the Special Issue Human Cancer Modeling in Zebrafish to Improve Our Understanding and Treatment)
►▼ Show Figures

Figure 1

14 pages, 3176 KiB  
Article
S1P1 Threonine 236 Phosphorylation Mediates the Invasiveness of Triple-Negative Breast Cancer and Sensitivity to FTY720
by Fabrice J. F. Laroche, Sheng Li, Ning Shen, Soo Kyung Hwang, Gina Nguyen, Wenling Yu, Chen Khuan Wong, Ryan J. Quinton, Jason N. Berman, Ching-Ti Liu, Anurag Singh, Neil J. Ganem, Sam Thiagalingam and Hui Feng
Cells 2023, 12(7), 980; https://doi.org/10.3390/cells12070980 - 23 Mar 2023
Cited by 2 | Viewed by 2478
Abstract
Hyperactive sphingosine 1-phosphate (S1P) signaling is associated with a poor prognosis of triple-negative breast cancer (TNBC). Despite recent evidence that links the S1P receptor 1 (S1P1) to TNBC cell survival, its role in TNBC invasion and the underlying mechanisms remain elusive. Combining analyses [...] Read more.
Hyperactive sphingosine 1-phosphate (S1P) signaling is associated with a poor prognosis of triple-negative breast cancer (TNBC). Despite recent evidence that links the S1P receptor 1 (S1P1) to TNBC cell survival, its role in TNBC invasion and the underlying mechanisms remain elusive. Combining analyses of human TNBC cells with zebrafish xenografts, we found that phosphorylation of S1P receptor 1 (S1P1) at threonine 236 (T236) is critical for TNBC dissemination. Compared to luminal breast cancer cells, TNBC cells exhibit a significant increase of phospho-S1P1 T236 but not the total S1P1 levels. Misexpression of phosphorylation-defective S1P1 T236A (alanine) decreases TNBC cell migration in vitro and disease invasion in zebrafish xenografts. Pharmacologic disruption of S1P1 T236 phosphorylation, using either a pan-AKT inhibitor (MK2206) or an S1P1 functional antagonist (FTY720, an FDA-approved drug for treating multiple sclerosis), suppresses TNBC cell migration in vitro and tumor invasion in vivo. Finally, we show that human TNBC cells with AKT activation and elevated phospho-S1P1 T236 are sensitive to FTY720-induced cytotoxic effects. These findings indicate that the AKT-enhanced phosphorylation of S1P1 T236 mediates much of the TNBC invasiveness, providing a potential biomarker to select TNBC patients for the clinical application of FTY720. Full article
(This article belongs to the Special Issue Human Cancer Modeling in Zebrafish to Improve Our Understanding and Treatment)
►▼ Show Figures

Figure 1

16 pages, 6147 KiB  
Article
Zebrafish Microenvironment Elevates EMT and CSC-Like Phenotype of Engrafted Prostate Cancer Cells
by Lanpeng Chen, Maciej Boleslaw Olszewski, Marianna Kruithof-de Julio and B. Ewa Snaar-Jagalska
Cells 2020, 9(4), 797; https://doi.org/10.3390/cells9040797 - 26 Mar 2020
Cited by 13 | Viewed by 4385
Abstract
To visually and genetically trace single-cell dynamics of human prostate cancer (PCa) cells at the early stage of metastasis, a zebrafish (ZF) xenograft model was employed. The phenotypes of intravenously transplanted fluorescent cells were monitored by high-resolution, single-cell intravital confocal and light-sheet imaging. [...] Read more.
To visually and genetically trace single-cell dynamics of human prostate cancer (PCa) cells at the early stage of metastasis, a zebrafish (ZF) xenograft model was employed. The phenotypes of intravenously transplanted fluorescent cells were monitored by high-resolution, single-cell intravital confocal and light-sheet imaging. Engrafted osteotropic, androgen independent PCa cells were extravasated from caudle vein, invaded the neighboring tissue, proliferated and formed experimental metastases around caudal hematopoietic tissue (CHT) in four days. Gene expression comparison between cells in culture and in CHT revealed that engrafted PCa cells responded to the ZF microenvironment by elevating expression of epithelial–mesenchymal transition (EMT) and stemness markers. Next, metastatic potentials of ALDHhi cancer stem-like cells (CSCs) and ALDHlow non-CSCs were analyzed in ZF. Engraftment of CSCs induced faster metastatic onset, however after six days both cell subpopulations equally responded to the ZF microenvironment, resulting in the same increase of stemness genes expression including Nanog, Oct-4 and Cripto. Knockdown of Cripto significantly reduced the vimentin/E-cadherin ratio in engrafted cells, indicating that Cripto is required for transduction of the microenvironment signals from the ZF niche to increase mesenchymal potential of cells. Targeting of either Cripto or EMT transcriptional factors Snail 1 and Zeb1 significantly suppressed metastatic growth. These data indicated that zebrafish microenvironment governed the CSC/EMT plasticity of human PCa cells promoting metastasis initiation. Full article
(This article belongs to the Special Issue Human Cancer Modeling in Zebrafish to Improve Our Understanding and Treatment)
►▼ Show Figures

Figure 1

Review

Jump to: Research

29 pages, 1244 KiB  
Review
Modeling Cancer Using Zebrafish Xenografts: Drawbacks for Mimicking the Human Microenvironment
by Pablo Cabezas-Sáinz, Alba Pensado-López, Bruno Sáinz, Jr. and Laura Sánchez
Cells 2020, 9(9), 1978; https://doi.org/10.3390/cells9091978 - 27 Aug 2020
Cited by 33 | Viewed by 8476
Abstract
The first steps towards establishing xenografts in zebrafish embryos were performed by Lee et al., 2005 and Haldi et al., 2006, paving the way for studying human cancers using this animal species. Since then, the xenograft technique has been improved in different ways, [...] Read more.
The first steps towards establishing xenografts in zebrafish embryos were performed by Lee et al., 2005 and Haldi et al., 2006, paving the way for studying human cancers using this animal species. Since then, the xenograft technique has been improved in different ways, ranging from optimizing the best temperature for xenografted embryo incubation, testing different sites for injection of human tumor cells, and even developing tools to study how the host interacts with the injected cells. Nonetheless, a standard protocol for performing xenografts has not been adopted across laboratories, and further research on the temperature, microenvironment of the tumor or the cell–host interactions inside of the embryo during xenografting is still needed. As a consequence, current non-uniform conditions could be affecting experimental results in terms of cell proliferation, invasion, or metastasis; or even overestimating the effects of some chemotherapeutic drugs on xenografted cells. In this review, we highlight and raise awareness regarding the different aspects of xenografting that need to be improved in order to mimic, in a more efficient way, the human tumor microenvironment, resulting in more robust and accurate in vivo results. Full article
(This article belongs to the Special Issue Human Cancer Modeling in Zebrafish to Improve Our Understanding and Treatment)
►▼ Show Figures

Figure 1

18 pages, 1367 KiB  
Review
From Tank to Treatment: Modeling Melanoma in Zebrafish
by William Tyler Frantz and Craig J Ceol
Cells 2020, 9(5), 1289; https://doi.org/10.3390/cells9051289 - 22 May 2020
Cited by 17 | Viewed by 4880
Abstract
Melanoma is the deadliest form of skin cancer and one of few cancers with a growing incidence. A thorough understanding of its pathogenesis is fundamental to developing new strategies to combat mortality and morbidity. Zebrafish—due in large part to their tractable genetics, conserved [...] Read more.
Melanoma is the deadliest form of skin cancer and one of few cancers with a growing incidence. A thorough understanding of its pathogenesis is fundamental to developing new strategies to combat mortality and morbidity. Zebrafish—due in large part to their tractable genetics, conserved pathways, and optical properties—have emerged as an excellent system to model melanoma. Zebrafish have been used to study melanoma from a single tumor initiating cell, through metastasis, remission, and finally into relapse. In this review, we examine seminal zebrafish studies that have advanced our understanding of melanoma. Full article
(This article belongs to the Special Issue Human Cancer Modeling in Zebrafish to Improve Our Understanding and Treatment)
►▼ Show Figures

Figure 1

28 pages, 666 KiB  
Review
Inflammatory Responses during Tumour Initiation: From Zebrafish Transgenic Models of Cancer to Evidence from Mouse and Man
by Abigail Elliot, Henna Myllymäki and Yi Feng
Cells 2020, 9(4), 1018; https://doi.org/10.3390/cells9041018 - 20 Apr 2020
Cited by 12 | Viewed by 5266
Abstract
The zebrafish is now an important model organism for cancer biology studies and provides unique and complementary opportunities in comparison to the mammalian equivalent. The translucency of zebrafish has allowed in vivo live imaging studies of tumour initiation and progression at the cellular [...] Read more.
The zebrafish is now an important model organism for cancer biology studies and provides unique and complementary opportunities in comparison to the mammalian equivalent. The translucency of zebrafish has allowed in vivo live imaging studies of tumour initiation and progression at the cellular level, providing novel insights into our understanding of cancer. Here we summarise the available transgenic zebrafish tumour models and discuss what we have gleaned from them with respect to cancer inflammation. In particular, we focus on the host inflammatory response towards transformed cells during the pre-neoplastic stage of tumour development. We discuss features of tumour-associated macrophages and neutrophils in mammalian models and present evidence that supports the idea that these inflammatory cells promote early stage tumour development and progression. Direct live imaging of tumour initiation in zebrafish models has shown that the intrinsic inflammation induced by pre-neoplastic cells is tumour promoting. Signals mediating leukocyte recruitment to pre-neoplastic cells in zebrafish correspond to the signals that mediate leukocyte recruitment in mammalian tumours. The activation state of macrophages and neutrophils recruited to pre-neoplastic cells in zebrafish appears to be heterogenous, as seen in mammalian models, which provides an opportunity to study the plasticity of innate immune cells during tumour initiation. Although several potential mechanisms are described that might mediate the trophic function of innate immune cells during tumour initiation in zebrafish, there are several unknowns that are yet to be resolved. Rapid advancement of genetic tools and imaging technologies for zebrafish will facilitate research into the mechanisms that modulate leukocyte function during tumour initiation and identify targets for cancer prevention. Full article
(This article belongs to the Special Issue Human Cancer Modeling in Zebrafish to Improve Our Understanding and Treatment)
►▼ Show Figures

Figure 1

24 pages, 2589 KiB  
Review
Zebrafish Avatars towards Personalized Medicine—A Comparative Review between Avatar Models
by Bruna Costa, Marta F. Estrada, Raquel V. Mendes and Rita Fior
Cells 2020, 9(2), 293; https://doi.org/10.3390/cells9020293 - 25 Jan 2020
Cited by 58 | Viewed by 9622
Abstract
Cancer frequency and prevalence have been increasing in the past decades, with devastating impacts on patients and their families. Despite the great advances in targeted approaches, there is still a lack of methods to predict individual patient responses, and therefore treatments are tailored [...] Read more.
Cancer frequency and prevalence have been increasing in the past decades, with devastating impacts on patients and their families. Despite the great advances in targeted approaches, there is still a lack of methods to predict individual patient responses, and therefore treatments are tailored according to average response rates. “Omics” approaches are used for patient stratification and choice of therapeutic options towards a more precise medicine. These methods, however, do not consider all genetic and non-genetic dynamic interactions that occur upon drug treatment. Therefore, the need to directly challenge patient cells in a personalized manner remains. The present review addresses the state of the art of patient-derived in vitro and in vivo models, from organoids to mouse and zebrafish Avatars. The predictive power of each model based on the retrospective correlation with the patient clinical outcome will be considered. Finally, the review is focused on the emerging zebrafish Avatars and their unique characteristics allowing a fast analysis of local and systemic effects of drug treatments at the single-cell level. We also address the technical challenges that the field has yet to overcome. Full article
(This article belongs to the Special Issue Human Cancer Modeling in Zebrafish to Improve Our Understanding and Treatment)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-7
Back to TopTop