Catchup: a mouse model for imaging-based tracking and modulation of neutrophil granulocytes

Hasenberg, Anja; Hasenberg, Mike; Männ, Linda; Neumann, Franziska; Borkenstein, Lars; Stecher, Manuel; Kraus, Andreas; Engel, Daniel R.; Klingberg, Anika; Seddigh, Pegah; Abdullah, Zeinab; Klebow, Sabrina; Engelmann, Swen; Reinhold, Annegret; Brandau, Sven; Seeling, Michaela; Waisman, Ari; Schraven, Burkhart; Göthert, Joachim R.; Nimmerjahn, Falk; Gunzer, Matthias

doi:10.1038/nmeth.3322

Cited by 208 publications

(217 citation statements)

References 43 publications

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“…Recently, a mouse model based on Ly6g-driven Cre recombinase was developed, the Catchup mouse, which includes a fluorescent reporter allowing the function of mature neutrophils to be monitored via in vivo imaging 206 . One value of this model stems from its ability to specifically delete neutrophil-derived molecules at later stages of these cells' differentiation.…”

Section: Discussionmentioning

confidence: 99%

Neutrophils in cancer: neutral no more

2016

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SummaryNeutrophils are indispensable antagonists of microbial infection and facilitators of wound healing. In the cancer setting, a newfound appreciation for neutrophils has come into view.The traditionally held belief that neutrophils are inert bystanders is being challenged by recent literature. Emerging evidence indicates that tumors manipulate neutrophils, sometimes early in their differentiation process, to create diverse phenotypic and functional polarization states able to alter tumor behavior. In this Review, we discuss the involvement of neutrophils in cancer initiation and progression, and their potential as clinical biomarkers and therapeutic targets. 2The name neutrophil -given to polymorphonuclear, granulocytic cells by Paul Ehrlich in the late 19th century -is based on the inability of these cells to retain acidic or basic dyes and for their preferential uptake of pH neutral dyes 1 . Although their neutral staining led to the identification of these cells, neutrophils in the cancer setting are anything but neutral.Neutrophils in tumor-bearing hosts can oppose or potentiate cancer progression. These two types of behavior are controlled by signals emanating from cancer cells or stromal cells within the tumor microenvironment, which educate neutrophils to execute the demise of the tumor or facilitate support networks that lead to its expansive spread. These functions can occur locally in or around the tumor microenvironment, as well as systemically in distant organs.Until the past few years, other immune cells such as macrophages have overshadowed the role of neutrophils in cancer. But recent studies and the development of new genetic tools have provided the cancer community with new insights into the profound influence of these dynamic cells by uncovering distinct capabilities for neutrophils throughout each step of carcinogenesis: from tumor initiation to primary tumor growth to metastasis.During these processes, neutrophils take on different phenotypes and sometimes opposing functions. Emerging evidence also indicates that these cells are highly influential, and are able to change the behavior of other tumor-associated cell types -primarily other immune cells. In this Review, we focus on how tumors manipulate the generation and release of neutrophils from the bone marrow. We discuss the mechanisms identified in animal models by which neutrophils participate in tumor initiation, growth and metastasis. Finally, we highlight the potential of these cells as clinical biomarkers and therapeutic targets. In humans, neutrophils are the most abundant immune cell population, representing 50-70% of all leukocytes. Over 10 11 neutrophils may be produced per day 2 , and tumors can increase this number by even more. Indeed, patients with various cancer types, including but not limited to breast, lung and colorectal cancer, often exhibit increased numbers of circulating neutrophils 3,4 . Recent studies have identified key pathways that tumors exploit to disrupt normal neutrophil homeostasis and these are discuss...

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Section: Discussionmentioning

confidence: 99%

Neutrophils in cancer: neutral no more

2016

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“…Indeed, retrograde migration of neutrophils, from the site of tissue perturbation, back to the circulation has been reported in the context of inflammation but still has to be proven in experimental animal models of cancer [127-129]. Recently, a new genetically engineered mouse model exhibited successful intravital imaging of neutrophils giving it an important advantage when, e.g., attempting to visualize neutrophil-retrograde migration [130]. …”

Section: Future Perspectives and Conclusionmentioning

confidence: 99%

Neutrophils: Critical components in experimental animal models of cancer

Hagerling

Werb

2016

Seminars in Immunology

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Neutrophils have a crucial role in tumor development and metastatic progression. The contribution of neutrophils in tumor development is multifaceted and contradictory. On the one hand, neutrophils prompt tumor inception, promote tumor development by mediating the initial angiogenic switch and facilitate colonization of circulating tumor cells, and on the other hand, have cytotoxic and anti-metastatic capabilities. Our understanding of the role of neutrophils in tumor development has greatly depended on different experimental animal models of cancer. In this review we cover important findings that have been made about neutrophils in experimental animal models of cancer, point to their advantages and limitations, and discuss novel techniques that can be used to expand our knowledge of how neutrophils influence tumor progression.

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“…Importantly, we have shown that the same rapid induction of motility also occurs in neutrophils within the bone marrow of mice in vivo after systemic application of human G-CSF. However, as opposed to the in vitro situation, increased neutrophil motility in vivo is maintained over several hours, because the production of migration-activating chemokines from endothelial cells and megakaryocytes is also induced by G-CSF in the bone marrow [6,7]. Both effects together lead to the rapid release of pre-existing mature neutrophils from the bone marrow to the circulation within hours after systemic G-CSF application in mice [6].…”

Section: G-csf Rapidly Induces Neutrophil Migrationmentioning

confidence: 99%

How Safe Is the Administration of Long-Acting Granulocyte Colony-Stimulating Factor in Cancer Patients?

2018

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Long-acting granulocyte colony-stimulating factor (G-CSF) preparations are increasingly used in the management of chemotherapy-associated neutropenia. Due to the fact that they only need to be administered once following chemotherapy, they are more convenient for patients and easier to use in the clinical routine for physicians than short-term G-CSF preparations. Although the efficacy of these growth factors is generally accepted, there remains some concern regarding their safety. In this article we address safety concerns for long-acting growth factors by providing basic information and available data around important clinical issues that may be helpful for the decision to use or not to use these factors in individual clinical situations. After a critical review of the literature, regarding theoretical considerations based on the physiology of hematopoiesis, data from clinical studies show that long-acting G-CSF preparations can be applied safely in approved indications and are broadly beneficial for patients at risk undergoing chemotherapy.

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Catchup: a mouse model for imaging-based tracking and modulation of neutrophil granulocytes

Cited by 208 publications

References 43 publications

Neutrophils in cancer: neutral no more

Neutrophils in cancer: neutral no more

Neutrophils: Critical components in experimental animal models of cancer

How Safe Is the Administration of Long-Acting Granulocyte Colony-Stimulating Factor in Cancer Patients?

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