Imaging innate immune responses at tumour initiation: new insights from fish and flies

Feng, Yi; Martin, Paul

doi:10.1038/nrc3979

Cited by 41 publications

(34 citation statements)

References 69 publications

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“…The model that we used represents a metastatic disease model, as human CM cells were injected into the circulation of the zebrafish embryos. 37 Using Ki67 staining, we showed that CM cells survived and proliferated inside the fish until at least 6 dpi. We furthermore observed that 58% to 64% of all engrafted embryos showed dissemination of the cells to the tail at 6 dpi, demonstrating a preference of all three cell lines for this site.…”

Section: Discussionmentioning

confidence: 89%

“…The zebrafish embryo can be used to study the interaction between the innate immune system (neutrophils and macrophages) and tumor cell behavior: this is one of the reasons why we set out to develop this CM model. 37,38 The mutations involved in CM are more similar to cutaneous melanoma than uveal melanoma. Cutaneous melanoma and CM harbor a B-RAF mutation, while in most uveal melanoma, GNAQ/GNA11 mutations occur.…”

Section: Discussionmentioning

confidence: 99%

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Evaluation of (fli:GFP) Casper Zebrafish Embryos as a Model for Human Conjunctival Melanoma

Pontes

Groenewoud

Cao

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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Citation: Pontes KCS, Groenewoud A, Cao J, Ataide LMS, Snaar-Jagalska E, Jager MJ. Evaluation of (fli:GFP) Casper zebrafish embryos as a model for human conjunctival melanoma. Invest Ophthalmol Vis Sci. 2017;58:6065-6071. DOI:10.1167/iovs.17-22023 PURPOSE. Conjunctival melanoma (CM) is a rare malignant disease that can lead to recurrences and metastases. There is a lack of effective treatments for the metastases, and we set out to develop a new animal model to test potential therapies. Zebrafish are being used as a model for many diseases, and our goal was to test whether this animal could be used to study CM. METHODS.Three human CM cell lines (CRMM-1 and CM2005.1, which both harbor a B-RAF mutation, and CRMM-2, which has an N-RAS mutation) were injected into the yolk sac, around the eye, and into the duct of Cuvier of transgenic (fli:GFP) Casper zebrafish embryos. Fluorescent and confocal images were taken to assess the phenotype and the behavior of engrafted cells and to test the effect of Vemurafenib as a treatment against CM.RESULTS. While the cells that had been injected inside the yolk sac died and those injected around the eye sporadically went into the circulation, the cells that had been injected into the duct of Cuvier colonized the zebrafish: cells from all three cell lines proliferated and disseminated to the eyes, where they formed clusters, and to the tail, where we noticed extravasation and micrometastases. Vemurafenib, a potent agent for treatment of B-RAF V600E-positive melanoma, inhibited outgrowth of CRMM-1 and CM2005.1 cells in a mutation-dependent way.CONCLUSIONS. The (fli:GFP) Casper zebrafish embryo can be used as an efficient animal model to study metastatic behavior of human CM cells and warrants further testing of drug efficacy to aid care of CM patients.

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Evaluation of (fli:GFP) Casper Zebrafish Embryos as a Model for Human Conjunctival Melanoma

Pontes

Groenewoud

Cao

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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“…To visualize melanoma and macrophage interactions, we took advantage of human-in-fish xenotransplantation. This approach has been a powerful tool to explore interactions between tumor cells and microenvironmental components because of the optical clarity of the larval fish, and the ease of introducing reporters that allow for the study of tumor cell behaviour at high resolution (Chapman et al, 2014; Feng and Martin, 2015; Lee et al, 2005; Stoletov et al, 2007; Wang et al, 2015; White et al, 2008). We adapted the human-in-fish xenotransplantation approach to be amenable to high resolution imaging by transplanting tumor cells into the larval hindbrain ventricle rather than near the yolk as has been previously described (Chapman et al, 2014; Stoletov et al, 2007; White et al, 2008) (Figure 1A, B).…”

Section: Resultsmentioning

confidence: 99%

Macrophage-Dependent Cytoplasmic Transfer during Melanoma Invasion In Vivo

et al. 2017

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Summary Interactions between tumor cells and tumor-associated macrophages play critical roles in the initiation of tumor cell motility. To capture the cellular interactions of the tumor microenvironment with high-resolution imaging, we directly visualized tumor cells and their interactions with macrophages in zebrafish. Live-imaging in zebrafish revealed that macrophages are dynamic, yet maintain sustained contact with tumor cells. Additionally, the recruitment of macrophages to tumor cells promotes tumor cell dissemination. Using a Cre/LoxP strategy, we found that macrophages transfer cytoplasm to tumor cells in zebrafish and mouse models. Remarkably, macrophage cytoplasmic transfer correlated with melanoma cell dissemination. We further found that macrophages transfer cytoplasm to tumor cells upon cell contact in vitro. Thus, we present a model in which macrophage/tumor cell contact allows for the transfer of cytoplasmic molecules from macrophages to tumor cells corresponding to increased tumor cell motility and dissemination.

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“…293 For example, inflammation is one of two new enabling characteristics of cancer. 111 Immune cells often make up most of the tumour mass, confounding standard efforts to monitor immunotherapy.…”

Section: Nuclear Medicine and Imagingmentioning

confidence: 99%

Future cancer research priorities in the USA: a Lancet Oncology Commission

Jaffee

Dang

Agus

et al. 2017

The Lancet Oncology

171

123

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We are in the midst of a technological revolution that is providing new insights into human biology and cancer. In this era of big data, we are amassing large amounts of information that is transforming how we approach cancer treatment and prevention. Enactment of the Cancer Moonshot within the 21st Century Cures Act in the USA arrived at a propitious moment in the advancement of knowledge, providing nearly US$2 billion of funding for cancer research and precision medicine. In 2016, the Blue Ribbon Panel (BRP) set out a roadmap of recommendations designed to exploit new advances in cancer diagnosis, prevention, and treatment. Those recommendations provided a high-level view of how to accelerate the conversion of new scientific discoveries into effective treatments and prevention for cancer. The US National Cancer Institute is already implementing some of those recommendations. As experts in the priority areas identified by the BRP, we bolster those recommendations to implement this important scientific roadmap. In this Commission, we examine the BRP recommendations in greater detail and expand the discussion to include additional priority areas, including surgical oncology, radiation oncology, imaging, health systems and health disparities, regulation and financing, population science, and oncopolicy. We prioritise areas of research in the USA that we believe would accelerate efforts to benefit patients with cancer. Finally, we hope the recommendations in this report will facilitate new international collaborations to further enhance global efforts in cancer control.

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Imaging innate immune responses at tumour initiation: new insights from fish and flies

Cited by 41 publications

References 69 publications

Evaluation of (fli:GFP) Casper Zebrafish Embryos as a Model for Human Conjunctival Melanoma

Evaluation of (fli:GFP) Casper Zebrafish Embryos as a Model for Human Conjunctival Melanoma

Macrophage-Dependent Cytoplasmic Transfer during Melanoma Invasion In Vivo

Future cancer research priorities in the USA: a Lancet Oncology Commission

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