Abstract:
:Signaling through chemokine receptor, C-X-C chemokine receptor type 4 (CXCR4) regulates essential processes in normal physiology, including embryogenesis, tissue repair, angiogenesis, and trafficking of immune cells. Tumors co-opt many of these fundamental processes to directly stimulate proliferation, invasion, and metastasis of cancer cells. CXCR4 signaling contributes to critical functions of stromal cells in cancer, including angiogenesis and multiple cell types in the tumor immune environment. Studies in animal models of several different types of cancers consistently demonstrate essential functions of CXCR4 in tumor initiation, local invasion, and metastasis to lymph nodes and distant organs. Data from animal models support clinical observations showing that integrated effects of CXCR4 on cancer and stromal cells correlate with metastasis and overall poor prognosis in >20 different human malignancies. Small molecules, Abs, and peptidic agents have shown anticancer efficacy in animal models, sparking ongoing efforts at clinical translation for cancer therapy. Investigators also are developing companion CXCR4-targeted imaging agents with potential to stratify patients for CXCR4-targeted therapy and monitor treatment efficacy. Here, pre-clinical studies demonstrating functions of CXCR4 in cancer are reviewed.
journal_name
J Leukoc Bioljournal_title
Journal of leukocyte biologyauthors
Luker GD,Yang J,Richmond A,Scala S,Festuccia C,Schottelius M,Wester HJ,Zimmermann Jdoi
10.1002/JLB.2BT1018-715RRsubject
Has Abstractpub_date
2020-10-26 00:00:00eissn
0741-5400issn
1938-3673pub_type
杂志文章,评审abstract::In RAW 264.7 cells, PKC-ε regulates FcγR-mediated phagocytosis. BMDM behave similarly; PKC-ε concentrates at phagosomes and internalization are reduced in PKC-ε⁻/⁻ cells. Two questions were asked: what is the role of PKC-ε? and what domains are necessary for PKC-ε concentration? Function was studied using BMDM and fru...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.1212634
更新日期:2013-07-01 00:00:00
abstract::The effect of endothelial cells (EC) on lymphocyte mitogen responses was examined. Irradiated or mitomycin C treated EC were co-cultured with allogeneic peripheral blood mononuclear cells (PBM), and proliferative responses to pokeweed mitogen (PWM) and phytohemagglutinin (PHA) were assessed by 3H-thymidine incorporati...
journal_title:Journal of leukocyte biology
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doi:10.1002/jlb.37.3.305
更新日期:1985-03-01 00:00:00
abstract::Cytohesin-1 and ARNO are guanine nucleotide-exchange factors (GEFs) for ADP-ribosylation factor (Arf). Here, we show that ARNO is expressed in HL-60 cells and established that granulocytic differentiation induced with Me2SO stimulated cytohesin-1 but not ARNO expression. Cytohesin-1 levels in HL-60 granulocytes were s...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
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更新日期:2002-04-01 00:00:00
abstract::Interleukin-1beta is a secreted protein that accumulates in the cytosol as an inactive precursor (pIL-1beta) before processing and release of biologically active protein. To understand the impact of this property on IL-1beta production, we examined the intracellular stability of pIL-1beta in lipopolysaccharide (LPS)-s...
journal_title:Journal of leukocyte biology
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更新日期:2000-07-01 00:00:00
abstract::The receptor for urokinase plasminogen activator (uPAR; CD87) is a 50- to 65-kDa glycosylphosphatidylinositol (GPI)-anchored glycoprotein expressed by leukocytes and tumor cells where it facilitates uPA-dependent, plasmin-mediated pericellular proteolysis during cellular invasion. Because uPAR is inducibly shed into c...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.64.2.203
更新日期:1998-08-01 00:00:00
abstract::Monocytes have been categorized in three main subpopulations based on CD14 and CD16 surface expression. Classical monocytes express the CD14(++)CD16(-)CCR2(+) phenotype and migrate to inflammatory sites by quickly responding to CCL2 signaling. Here, we identified and characterized the expansion of a novel monocyte sub...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.1111579
更新日期:2012-05-01 00:00:00
abstract::We report the systematic use of large-scale cDNA microarrays to study the gene expression profiles of primary human peripheral blood monocytes (MONO) in comparison with in vitro-differentiated, M-CSF-induced MONO-derived macrophages (MAC) and primary human alveolar MAC (AM), obtained by bronchoalveolar lavage from the...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0206124
更新日期:2007-01-01 00:00:00
abstract::T cell Ig and mucin domain-containing molecule 3 (Tim-3) has been found to play important roles in autoimmune diseases, but whether Tim-3-mediated engulfment of apoptotic cells is involved in systemic lupus erythematosus (SLE) remains to be elucidated. In this study, we verified the role of human Tim-3 (hTim-3) as the...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.3HI0117-005RR
更新日期:2017-12-01 00:00:00
abstract::Osteopontin is an RGD-containing bone matrix protein with cytokine-like functions that is associated with early stages of Th1-mediated diseases. Although the function of osteopontin in these responses is unknown, it is expressed by activated T cells and macrophages and can costimulate T cell proliferation. Studies hav...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:
更新日期:2000-10-01 00:00:00
abstract::Macrophages play major roles in the onset of immune responses and inflammation by inducing a variety of cytokines such as TNF and IFN-beta. The pathogen-associated molecular pattern, polyinosinic-polycytidylic acid [poly(I:C)], and LPS were used to study type-I IFN and TNF responses in human macrophages. Additionally,...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0607412
更新日期:2008-05-01 00:00:00
abstract::Underlying acquired immunity to the fungus Candida albicans is usually present in adult immunocompetent individuals and is presumed to prevent mucosal colonization progressing to symptomatic infection. Exploration of immunological events leading to Candida resistance or susceptibility has indicated the central role of...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:
更新日期:2000-08-01 00:00:00
abstract::Dendritic cells (DC) are professional antigen-presenting cells that are used in vaccine approaches to cancer. Classically, mature monocyte-derived DC are generated in vitro in the presence of interleukin (IL)-4, granulocyte macrophage-colony stimulating factor, and inflammatory cytokines (G4-DC). Recently, it has been...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0105052
更新日期:2005-10-01 00:00:00
abstract::Dendritic cell (DC) and DC-derived exosomes (EXO) have been used extensively for tumor vaccination. However, its therapeutic efficiency is limited to only production of prophylactic immunity against tumors. T cells can uptake DC-released EXO. However, the functional effect of transferred exosomal molecules on T cells ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0407249
更新日期:2007-10-01 00:00:00
abstract::The T-box transcription factor Eomes is expressed in cytotoxic immune cells and plays an important role in development, maintenance, and function of these cell types. Identification and separation of cells with differential Eomes expression would allow for better understanding of the transcriptional program governing ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0812400
更新日期:2013-02-01 00:00:00
abstract::Matrix metalloproteinases-2 and -9 (MMP-2/9) are critically involved in degradation of extracellular matrix, and their inhibition is discussed as a promising strategy against hepatic ischemia-reperfusion (I/R) injury. Here, we analyzed the role of MMP-2 and -9 for leukocyte migration and tissue injury in sham-operated...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0805468
更新日期:2006-06-01 00:00:00
abstract::TLRs act as sentinels in professional immune cells to detect and initiate the innate immune response to pathogen challenge. TLR4 is a widely expressed TLR, responsible for initiating potent immune responses to LPS. TRAM acts to bridge TLR4 with TRIF, orchestrating the inflammatory response to pathogen challenge. We ha...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.2A0913-487R
更新日期:2014-09-01 00:00:00
abstract::This study tested the hypothesis that eotaxins (CCL11, CCL24, and CCL26) and IL-5 contribute to eosinophil recruitment to the intestine in UC and that intestinal macrophages are important producers of CCL11 in this disease. Peripheral blood and rectal biopsy samples were obtained from patients with active (n=18) and q...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.1212640
更新日期:2013-11-01 00:00:00
abstract::Our previous studies demonstrated that i.p. injection of late apoptotic P388 cells caused phagocytosis by macrophages and transient infiltration of neutrophils into the peritoneal cavity. As neutrophils are known to function as effectors as well as regulators in the immune response, we examined the roles of infiltrati...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0606399
更新日期:2007-02-01 00:00:00
abstract::Microbicidal activity of neutrophils is usually measured by colony-counting techniques after cell lysis in distilled water. While studying the effect of the reduced nicotinamide adenine dinucleotide phosphate-oxidase inhibitor diphenyleneiodonium (DPI) on the staphylocidal activity of neutrophils, we obtained inconsis...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0605338
更新日期:2006-01-01 00:00:00
abstract::Rats were injected with phenylhydrazine (PHZ) for periods of up to 6 months, during which time a marked leukocytosis was induced. The highest leukocyte counts occurred within 4-5 days following injection. An initial injection of 4 mg/100 gm body weight evoked a mean total leukocyte count of 129 X 10(3) cells/microlite...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.39.1.37
更新日期:1986-01-01 00:00:00
abstract::Naïve T cells, when activated by specific antigen and cytokines, up-regulate adhesion molecules as well as chemokine receptors on their surface, which allows them to migrate to inflamed tissues. Human studies have shown that CXCR3 is one of the chemokine receptors that is induced during T cell activation. Moreover, CX...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.1102573
更新日期:2003-06-01 00:00:00
abstract::The last 10-15 years have witnessed a revolution in treating multiple myeloma, an incurable cancer of Ab-producing plasma cells. Advances in myeloma therapy were ushered in by novel agents that remodel the myeloma immune microenvironment. The first generation of novel agents included immunomodulatory drugs (thalidomid...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:10.1189/jlb.3MR1116-468R
更新日期:2017-08-01 00:00:00
abstract::The aim of the study was to elucidate the effect of lipopolysaccharide (LPS) administration in vivo (Escherichia coli endotoxin, 1 mg/kg body weight) on the expression and cellular activity of glucose-6-phosphate dehydrogenase (G6PDH, EC 1.1.1.49), the rate-limiting enzyme of the hexose monophosphate shunt in hepatic ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
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更新日期:1994-10-01 00:00:00
abstract::In previous studies, macrophages have been shown to influence in vitro colony formation by erythroid progenitors (CFU-E). To determine whether the origin of the macrophages influences their effects on in vitro erythropoiesis, plasma clot cultures of CFU-E were grown over adherent monolayers of macrophages from various...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.36.5.581
更新日期:1984-11-01 00:00:00
abstract::Cytokines of the GM-CSF family signal via the same receptor subunit (βc) and, thus, have overlapping effects on cells that express all cytokine-specific α-chains (IL-3Rα, IL-5Rα, GM-CSFRα), such as human basophils, whose rapid effector functions are similarly enhanced by IL-3, IL-5, and GM-CSF. However, previous work ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.2A0715-292RR
更新日期:2017-01-01 00:00:00
abstract::Immune-checkpoint blockade therapy with antibodies targeting CTLA-4 and PD-1 has revolutionized melanoma treatment by eliciting responses that can be remarkably durable and is now advancing to other malignancies. However, not all patients respond to immune-checkpoint inhibitors. Extensive preclinical evidence suggests...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:10.1189/jlb.5RI0116-013RR
更新日期:2016-08-01 00:00:00
abstract::Several alterations in the expression of immune-related transcripts were identified recently in the degenerating retina of the retinoschisin knockout (Rs1h(-/Y)) mouse, including the strong expression of the adaptor protein Dap12. As Dap12 is found in leukocytes, we hypothesized that its disease-related expression may...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0707447
更新日期:2007-12-01 00:00:00
abstract::Apoptosis of polymorphonuclear leukocytes (PMNs) is a critical step in the resolution of tissue inflammation. PMN apoptosis has been studied extensively in vitro, and diverse inflammatory mediators have been shown to modulate the process. The reported effects of interleukin-6 (IL-6) on PMN apoptosis are inconsistent; ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.58.5.582
更新日期:1995-11-01 00:00:00
abstract::The transmembrane form of tumor necrosis factor (mTNF), expressed on activated monocytes (MO) and macrophages (MPhi), is able to induce apoptosis in human endothelial cells (EC). Apoptosis is mediated by two distinct mechanisms: direct cell contact and a yet-unidentified soluble protein, death factor X. In addition, m...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0703343
更新日期:2004-02-01 00:00:00
abstract::Microorganisms interact with the immune system in multiple ways. In an interaction between a microorganism and its host, the defense of the host does not go unchallenged. Microorganisms have for decades been suspected of possessing the capabilities of hiding from and escaping the consequences of immune surveillance. E...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:10.1002/jlb.62.4.415
更新日期:1997-10-01 00:00:00