Role of Bv8 in neutrophil-dependent angiogenesis in a transgenic model of cancer progression

Shojaei, Farbod; Singh, Mallika; Thompson, Jennifer; Ferrara, Napoleone

doi:10.1073/pnas.0712185105

Cited by 280 publications

(215 citation statements)

References 38 publications

(60 reference statements)

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“…In other studies, co-injection of cancer cell lines with neutrophils isolated from tumor-bearing mice increased tumor growth and angiogenesis 126 , underscoring their ability to perpetuate proliferation. Several mitogenic and pro-angiogenic molecules have been implicated in neutrophil-driven tumor growth including elastase, prokineticin 2 (PROK2, also known as BV8) and MMP9 115,120,[126][127][128][129] . Immunosuppression -through amino acid depletion or specific cytokine release -is another predominant mechanism neutrophils use to facilitate tumor …”

Section: Neutrophils and Tumor Growthmentioning

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: Neutrophils and Tumor Growthmentioning

confidence: 99%

Neutrophils in cancer: neutral no more

2016

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“…TANs were shown to support tumor growth by producing angiogenic factors and matrix-degrading enzymes [8,57,64,252,264,277]. Neutrophils were also shown to promote the acquisition of a metastatic phenotype [265] and to suppress antitumor immune responses [278].…”

Section: Neutrophils At the Primary Tumor Sitementioning

confidence: 99%

The Multifaceted Roles Neutrophils Play in the Tumor Microenvironment

Sionov

Fridlender

Granot

2014

Cancer Microenvironment

336

261

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Neutrophils are myeloid cells that constitute 50-70 % of all white blood cells in the human circulation. Traditionally, neutrophils are viewed as the first line of defense against infections and as a major component of the inflammatory process. In addition, accumulating evidence suggest that neutrophils may also play a key role in multiple aspects of cancer biology. The possible involvement of neutrophils in cancer prevention and promotion was already suggested more than half a century ago, however, despite being the major component of the immune system, their contribution has often been overshadowed by other immune components such as lymphocytes and macrophages. Neutrophils seem to have conflicting functions in cancer and can be classified into anti-tumor (N1) and pro-tumor (N2) sub-populations. The aim of this review is to discuss the varying nature of neutrophil function in the cancer microenvironment with a specific emphasis on the mechanisms that regulate neutrophil mobilization, recruitment and activation.

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“…Genetic or pharmacological inhibition of TNF suppresses the development as a critical regulator of CD11b + Gr1 + cell mobilization from the bone marrow, and CD11b + Gr1 + cell-mediated tumor angiogenesis (Shojaei et al, 2008). Anti-Bv8 antibody treatment resulted in a significant decrease of tumor growth and a reduction in CD11b + Gr1 + cell mobilization from the bone marrow.…”

Section: Tumor Necrosis Factor (Tnf)mentioning

confidence: 99%