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Nakashima, Emi; Mukaida, Naofumi; Kubota, Yoshi; Kuno, Kouji; Yasumoto, Keiichi; Ichimura, Fujio; Nakanishi, Isao; Miyasaka, Masayuki; Matsushima, Kouji

doi:10.1023/a:1016276613684

Cited by 60 publications

(6 citation statements)

References 12 publications

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“…For example, CCL2 (MCP-1), which is overexpressed in a wide range of cancers [234], is associated with poor prognosis in breast, colorectal, cervical and thyroid cancers [235][236][237][238][239]. Tumor-derived CCL2 plays a pro-tumor role by recruiting inflammatory monocytes to pulmonary metastases [240] and MDSCs to the tumor microenvironment [241], as well as promoting angiogenesis [242], tumor cell proliferation [243] and migration [244]. On the other hand, CCL2 prevents apoptosis of neutrophils [245] and activates neutrophils in the pre-metastatic lung towards an anti-tumor phenotype where they produce H 2 O 2 to kill disseminated tumor cells [32,66], suggesting a dual role of this chemokine.…”

Section: Neutrophil Activation In Cancermentioning

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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Section: Neutrophil Activation In Cancermentioning

confidence: 99%

The Multifaceted Roles Neutrophils Play in the Tumor Microenvironment

Sionov

Fridlender

Granot

2014

Cancer Microenvironment

336

261

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“…Under physiologic conditions, the CCL2/CCR2 chemokine axis plays an important role in the mobilization of inflammatory monocytes from the bone marrow to the blood [36]. Studies had proposed a dual role of CCL2 on tumor growth, and CCL2 can be protective in some tumor models but destructive in others [37, 38]. Overexpression of CCL2 by tumor cells can lead to their destruction by an infiltrate of activated mononuclear cells and may indicate a more favorable prognosis.…”

Section: Recruitment and Characteristics Of Tam In Pancreatic Cancermentioning

confidence: 99%

Targeting tumor-associated macrophages to combat pancreatic cancer

et al. 2016

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The tumor microenvironment is replete with cells that evolve with and provide support to tumor cells during the transition to malignancy. The hijacking of the immune system in the pancreatic tumor microenvironment is suggested to contribute to the failure to date to produce significant improvements in pancreatic cancer survival by various chemotherapeutics. Regulatory T cells, myeloid derived suppressor cells, and fibroblasts, all of which constitute a complex ecology microenvironment, can suppress CD8+ T cells and NK cells, thus inhibiting effector immune responses. Tumor-associated macrophages (TAM) are versatile immune cells that can express different functional programs in response to stimuli in tumor microenvironment at different stages of pancreatic cancer development. TAM have been implicated in suppression of anti-tumorigenic immune responses, promotion of cancer cell proliferation, stimulation of tumor angiogenesis and extracellular matrix breakdown, and subsequent enhancement of tumor invasion and metastasis. Many emerging agents that have demonstrated efficacy in combating other types of tumors via modulation of macrophages in tumor microenvironments are, however, only marginally studied for pancreatic cancer prevention and treatment. A better understanding of the paradoxical roles of TAM in pancreatic cancer may pave the way to novel preventive and therapeutic approaches. Here we give an overview of the recruitment and differentiation of macrophages, TAM and pancreatic cancer progression and prognosis, as well as the potential preventive and therapeutic targets that interact with TAM for pancreatic cancer prevention and treatment.

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“…In human breast cancer, it was reported that CCL2 levels in the excised breast cancer tissue were correlated significantly with the level of vascular endothelial growth factor (VEGF), thymidine phosphorylase, TNFa and IL-8, which are potent angiogenic factors (94). Transfection of colon cancer cells with the CCL2 gene induces angiogenesis in a murine model (95). It has been demonstrated that both CCL2 and VEGF expression positively correlates with TAM infiltration and angiogenesis in breast cancer (96).…”

Section: Ccl2 In Prostate Cancermentioning

confidence: 99%