Genetic Models of Leukemia in Zebrafish

Baeten, Jeremy T.; Jong, Jill L. O. de

doi:10.3389/fcell.2018.00115

Cited by 24 publications

(17 citation statements)

References 112 publications

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“…Compared with other animal models, zebrafish provides a promising opportunity to monitor the dissemination and metastasis of single tumor cell owing to these advantages including large number of transparent eggs, rapid external development, immune-privileged feature, and less raised cost [20,21]. Recently, a series of zebrafish cancer models had been developed including uveal melanoma model [22], conjunctival melanoma model [23], glioma model [24], breast cancer model [25], malignant melanoma model [26], liposarcoma cancer model [27], and leukemia model [28]. Furthermore, zebrafish can absorb small molecular compounds from water and play an important role in efficiently and easily screening a large number of anticancer compounds [29].…”

Section: Introductionmentioning

confidence: 99%

Knockdown of Matrix Metallopeptidase 9 Inhibits Metastasis of Oral Squamous Cell Carcinoma Cells in a Zebrafish Xenograft Model

Wen

Yin

et al. 2020

BioMed Research International

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Destruction of extracellular matrix (ECM) is one of the basic steps of tumor invasion and metastasis. Matrix metalloproteinase (MMP) 9, a kind of zinc-ion-dependent endopeptidase, can degrade almost all protein components in the ECM, destroy the histological barrier of tumor cell invasion, and play a key role in tumor invasion and metastasis. The role of MMP-9 in tumor invasion and metastasis has attracted increasing attention and is considered the main proteolytic enzyme in this process. Although the overexpression of MMP-9 was detected in Oral squamous cell carcinoma (OSCC) tissues, further basic studies in vivo and in vitro are needed to investigate the role of MMP-9 in OSCCs and provide scientific validation. In this research, we developed a novel OSCC zebrafish xenograft model to study the role of the MMP-9 gene in oral carcinogenesis. Firstly, the MMP-9/shRNA lentiviral clone and control virus were constructed and transfected into OSCC cells. Then, the decreasing expression of MMP-9 was verified by RT-PCR and immunocytochemistry. Cell proliferation was detected by MTT assay. Colony formation was evaluated by colony formation assay. Cell invasion was evaluated using transwell invasion assay in vitro. In addition, OSCC cells with MMP-9/shRNA knockdown and control vector were injected into zebrafish and an OSCC tumor model in zebrafish was established to evaluate invasion and metastasis in vivo. Knockdown of MMP-9 gene by shRNA could inhibit OSCC cell growth and clone formation and markedly suppress cell invasion in vitro. And the knockdown of the MMP-9 gene could also significantly decrease the metastatic distance and number of metastatic tumor cells or lesions in vivo and suppress the metastasis rate in xenografted zebrafish. Taken together, these evidences indicated that the knockdown of MMP-9 might suppress OSCC cell invasion and metastasis in vivo and in vitro. The MMP-9 gene may be a promising therapeutic target for OSCCs in the future.

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Section: Introductionmentioning

confidence: 99%

Knockdown of Matrix Metallopeptidase 9 Inhibits Metastasis of Oral Squamous Cell Carcinoma Cells in a Zebrafish Xenograft Model

Wen

Yin

et al. 2020

BioMed Research International

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“…46 Regardless, these tumors present a new opportunity to study B-ALL in zebrafish, a tumor type with few animal models. 47 Another closely related model utilizing the human MYC oncogene was also recently demonstrated by Frazer’s team to produce both pre-B-ALL and T-ALL. 48 Analysis of our own RNA-sequencing data showed a clear difference in expression of putative B- and T-cell genes between individual tumors, suggesting that ALL of both B- and T-cell origin are included in our dataset ( Online Supplementary Figure S1 ).…”

Section: Discussionmentioning

confidence: 91%

The side population enriches for leukemia-propagating cell activity and Wnt pathway expression in zebrafish acute lymphoblastic leukemia

Baeten¹,

Waarts²,

Pruitt³

et al. 2019

Haematologica

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Cancer stem cells have been strongly linked to resistance and relapse in many malignancies. However, purifying them from within the bulk tumor has been challenging, so their precise genetic and functional characteristics are not well defined. The side population assay exploits the ability of some cells to efflux Hoechst dye via ATP-binding cassette transporters. Stem cells have increased expression of these transporters and this assay has been shown to enrich for stem cells in various tissues and cancers. This study identifies the side population within a zebrafish model of acute lymphoblastic leukemia and correlates the frequency of side population cells with the frequency of leukemia stem cells (more precisely referred to as leukemia-propagating cells within our transplantation model). In addition, the side population within the leukemia evolves with serial transplantation, increasing in tandem with leukemia-propagating cell frequency over subsequent generations. Sorted side population cells from these tumors are enriched for leukemia-propagating cells and have enhanced engraftment compared to sorted non-side population cells when transplanted into syngeneic recipients. RNA-sequencing analysis of sorted side population cells compared to non-side population cells identified a shared expression profile within the side population and pathway analysis yielded Wnt-signaling as the most overrepresented. Gene set enrichment analysis showed that stem cell differentiation and canonical Wnt-signaling were significantly upregulated in the side population. Overall, these results demonstrate that the side population in zebrafish acute lymphoblastic leukemia significantly enriches for leukemia-propagating cells and identifies the Wnt pathway as a likely genetic driver of leukemia stem cell fate.

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“…They display many appealing features—easy manipulation with transparent embryos and the capacity to carry out large-scale genetic and chemical screens, allowing convenient genetic manipulation and in vivo imaging of normal and aberrant hematopoiesis [53]. The majority of hematological malignancies modeled by zebrafish represent lymphoblastic and myeloid leukemias where the transgenic lines express oncogenic fusion genes and mutations commonly found in patients [54]. MPN modeling in zebrafish introduced jak2a V581F (an ortholog of human JAK2 V617F), which shared features with human PV [55].…”

Section: Experimental Models Of Mpnmentioning

confidence: 99%

Experimental Modeling of Myeloproliferative Neoplasms

Lanikova

Babošová

Prchal

2019

Genes

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Myeloproliferative neoplasms (MPN) are genetically very complex and heterogeneous diseases in which the acquisition of a somatic driver mutation triggers three main myeloid cytokine receptors, and phenotypically expresses as polycythemia vera (PV), essential thrombocytosis (ET), and primary myelofibrosis (PMF). The course of the diseases may be influenced by germline predispositions, modifying mutations, their order of acquisition and environmental factors such as aging and inflammation. Deciphering these contributory elements, their mutual interrelationships, and their contribution to MPN pathogenesis brings important insights into the diseases. Animal models (mainly mouse and zebrafish) have already significantly contributed to understanding the role of several acquired and germline mutations in MPN oncogenic signaling. Novel technologies such as induced pluripotent stem cells (iPSCs) and precise genome editing (using CRISPR/Cas9) contribute to the emerging understanding of MPN pathogenesis and clonal architecture, and form a convenient platform for evaluating drug efficacy. In this overview, the genetic landscape of MPN is briefly described, with an attempt to cover the main discoveries of the last 15 years. Mouse and zebrafish models of the driver mutations are discussed and followed by a review of recent progress in modeling MPN with patient-derived iPSCs and CRISPR/Cas9 gene editing.

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Genetic Models of Leukemia in Zebrafish

Cited by 24 publications

References 112 publications

Knockdown of Matrix Metallopeptidase 9 Inhibits Metastasis of Oral Squamous Cell Carcinoma Cells in a Zebrafish Xenograft Model

Knockdown of Matrix Metallopeptidase 9 Inhibits Metastasis of Oral Squamous Cell Carcinoma Cells in a Zebrafish Xenograft Model

The side population enriches for leukemia-propagating cell activity and Wnt pathway expression in zebrafish acute lymphoblastic leukemia

Experimental Modeling of Myeloproliferative Neoplasms

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