Overexpression of CXCL5 Is Associated With Poor Survival in Patients With Pancreatic Cancer

Li, Aihua; King, Jonathan C.; Moro, Aune; Sugi, Mark; Dawson, David W.; Kaplan, Jeffrey B.; Li, Gang; Lu, Xuyang; Strieter, Robert M.; Burdick, Marie D.; Go, Vay Liang W.; Reber, Howard A.; Eibl, Guido; Hines, Oscar J.

doi:10.1016/j.ajpath.2010.11.058

Cited by 146 publications

(125 citation statements)

References 41 publications

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“…These authors also performed xenograft assays in nude mice, in which they used shRNA downregulation of CXCL5 or antibody-mediated neutralization of CXCR2 and showed attenuation of pancreatic tumor cell growth. They also demonstrated that CXCL5 derived angiogenesis development was ERK, AKT and signal transducer and activator of transcription mediated signaling pathways [156] . Moreover, in a clinical study that analyzed 52 PACs and 52 pancreatic neuroendocrine tumors, Hussain et al [157] found that expression of CXCL8 and its receptors CXCR1/2 were significantly upregulated compared to normal pancreatic tissues, a finding confirmed by immunohistochemistry and qRT-PCR.…”

Section: Pancreasmentioning

confidence: 99%

“…Furthermore, another report suggests that CXCL5 may be a possible prognostic biomarker for pancreatic cancer. Li et al [156] reported that overexpression of CXCL5 is correlated with poorer tumor differentiation, advanced clinical stage, and shorter patient survival. These authors also performed xenograft assays in nude mice, in which they used shRNA downregulation of CXCL5 or antibody-mediated neutralization of CXCR2 and showed attenuation of pancreatic tumor cell growth.…”

Section: Pancreasmentioning

confidence: 99%

“…Correlated with poorer tumor differentiation, advanced clinical stage, and shorter patient survival, and ERK, AKT and STAT mediated angiogenesis [156] CXCL8, CXCR1/2 Upregulation in adenocarcinomas and neuroendocrine tumors [157] CXCL12, CXCR4 Downregulation of CXCL12 and upregulation of CXCR4 in tumors. CXCL12 correlated with MVD but not with MLVD, while CXCR4 showed opposite pattern [158] CXCR4, CXCR7 CXCR7 associated with tumor grade, inversely associated with tumor size, and possibly associated with tumor progression and differentiation but not with CXCR4 [159] …”

Section: Cxcl5mentioning

confidence: 99%

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Chemokines, chemokine receptors and the gastrointestinal system

Miyazaki¹,

Takabe²,

Yeudall³

2013

WJG

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Core tip: The chemokine network makes an attractive target for therapeutic intervention in many tumor types, including those of the gastrointestinal tract. However, we need to define more selective and specific targets, to minimize systemic side effects during treatment. INTRODUCTION Cancer development and progression in the gastrointestinal tractCancer is a disease in which normal cells acquire genetic and epigenetic abnormalities [1,2] , leading to disorientation of conventional processes for the maintenance of normal cell physiology. These aberrant genetic and epigenetic modifications to the normal cell induce abnormal cell motility, proliferation, and survival, eventually enabling these cells to invade into adjacent tissues and even to migrate to regional or distant organs where they may grow continuously as metastatic lesions [3] . For many cancer patients, metastasis is generally the major cause of disease-related death [4,5] . Therefore, it is indispensable to elucidate the basic molecular mechanisms of tumor development to identify effective therapeutic targets, which can possibly reduce the side-effects of treatment, and define useful molecular markers for early detection and prediction of disease course. Especially, the newly emerged concept of personalized medicine may require in-depth assessment of potential therapeutic molecular target(s) in each individual case through analysis of sig- REVIEW Chemokines, chemokine receptors and the gastrointestinal system AbstractThe biological properties of tumor cells are known to be regulated by a multitude of cytokines and growth factors, which include epidermal growth factor receptor agonists and members of the transforming growth factor β family. Furthermore, the recent explosion of research in the field of chemokine function as mediators of tumor progression has led to the possibility that these small, immunomodulatory proteins also play key roles in carcinogenesis and may, therefore, be potential targets for novel therapeutic approaches. In this review, we will summarize recently reported findings in chemokine biology with a focus on the gastrointestinal tract.

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Section: Pancreasmentioning

confidence: 99%

Section: Pancreasmentioning

confidence: 99%

Section: Cxcl5mentioning

confidence: 99%

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Chemokines, chemokine receptors and the gastrointestinal system

Miyazaki¹,

Takabe²,

Yeudall³

2013

WJG

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“…16 CXCL5 binds with CXCR1 and CXCR2 and activates MAP kinase and PI3 kinase signaling pathways. 17 It has been reported that CXCL5 levels are significantly increased in rheumatoid arthritis. 18 Moreover, inflammatory cytokine IL1b has been shown to induce CXCL5 expression by activation of NF-kB and CREB.…”

mentioning

confidence: 99%

“…16 CXCL5 binds with CXCR1 and CXCR2 and activates MAP kinase and PI3 kinase signaling pathways. 17 It has been reported that CXCL5 levels are significantly increased in …”

mentioning

confidence: 99%

CXCL5 stimulation of RANK ligand expression in Paget's disease of bone

Sundaram¹,

Rao

Ries

et al. 2013

Laboratory Investigation

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Paget's disease of bone (PDB) is a chronic focal skeletal disorder that affects 2-3% of the population over 55 years of age. PDB is marked by highly localized areas of bone turnover with increased osteoclast activity. Evidence suggests a functional role for measles virus nucleocapsid protein (MVNP) in the pathogenesis of PDB. In the present study, we identified elevated levels (B180-fold) of CXCL5 mRNA expression in bone marrow cells from patients with PDB compared with that in normal subjects. In addition, CXCL5 levels are increased (five-fold) in serum samples from patients with PDB. Furthermore, MVNP transduction in human bone marrow monocytes significantly increased CXCL5 mRNA expression. Realtime PCR analysis showed that CXCL5 stimulation increased (6.8-fold) RANKL mRNA expression in normal human bone marrow-derived stromal (SAKA-T) cells. Moreover, CXCL5 increased (5.2-fold) CXCR1 receptor expression in these cells. We further showed that CXCL5 treatment elevated the expression levels of phospho-ERK1/2 and phospho-p38. CXCL5 also significantly increased phosphorylation of CREB (cAMP response element-binding) in bone marrow stromal/preosteoblast cells. Chromatin immuneprecipitation (ChIP) assay confirmed phospho-CREB binding to RANKL gene promoter region. Further, the suppression of p-CREB expression by the inhibitors of ERK1/2, p38 and PKA significantly decreased CXCL5 stimulation of hRANKL gene promoter activity. Thus, our results suggest that CREB is a downstream effector of CXCL5 signaling and that increased levels of CXCL5 contribute to enhanced levels of RANKL expression in PDB. Paget's disease of bone (PDB) is characterized by highly localized areas of bone turnover with increased osteoclast (OCL) activity followed by poor quality new bone formation due to an exaggerated osteoblast response. Approximately 1% of patients with PDB develop osteosarcoma. 1 PDB is inherited as an autosomal dominant trait with genetic heterogeneity and affects 2-3% of the population over the age of 55 years. Both genetic and environmental factors are involved in the pathogenesis of PDB. Mutations in the ubiquitin-associated domain of sequestosome 1 (SQSTM1/p62) have been identified at 40% in familial and 10% in sporadic cases. 2 Environmental factors such as paramyxoviruses are implicated in PDB. 3 We have previously detected the expression of measles virus nucleocapsid (MVNP) transcripts in OCL from patients with PDB. 4 Moreover, the expression of MVNP in OCL precursors develops pagetic OCL in mice. 5 Receptor activator for nuclear factor-kB ligand (RANKL) is expressed by marrow stromal/osteoblast cells in response to several osteotropic factors such as 1,25 dihydroxy vitamin D 3 , parathyroid hormone (PTH), prostaglandin E 2 and interleukin 1b (IL-1b). 6-8 RANKL-RANK signaling is critical for osteoclast differentiation/bone resorption activity. Enhanced levels of RANKL are associated with PDB. 9,10 In addition, elevated levels of IL-6, macrophage colony-stimulating factor (M-CSF) and endothelin-1 have been reported in PD...

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CXCL5/CXCR2 axis in tumor microenvironment as potential diagnostic biomarker and therapeutic target

Zhang

Wang

Sun

et al. 2020

Cancer Communications

121

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The components of the tumor microenvironment (TME) in solid tumors, especially chemokines, are currently attracting much attention from scientists. C-X-C motif chemokine ligand 5 (CXCL5) is one of the important chemokines in TME. Overexpression of CXCL5 is closely related to the survival time, recurrence and metastasis of cancer patients. In TME, CXCL5 binds to its receptors, such as C-X-C motif chemokine receptor 2 (CXCR2), to participate in the recruitment of immune cells and promote angiogenesis, tumor growth, and metastasis. The CXCL5/CXCR2 axis can act as a bridge between tumor cells and host cells in TME. Blocking the transmission of CXCL5/CXCR2 signals can increase the sensitivity and effectiveness of immunotherapy and slow down tumor progression. CXCL5 and CXCR2 are also regarded as biomarkers for predicting prognosis and molecular targets for customizing the treatment. In this review, we summarized the current literature regarding the biological functions and clinical significance of CXCL5/CXCR2 axis in TME. The possibility to use CXCL5 and CXCR2 as potential prognostic biomarkers and therapeutic targets in cancer is also discussed

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Overexpression of CXCL5 Is Associated With Poor Survival in Patients With Pancreatic Cancer

Cited by 146 publications

References 41 publications

Chemokines, chemokine receptors and the gastrointestinal system

Chemokines, chemokine receptors and the gastrointestinal system

CXCL5 stimulation of RANK ligand expression in Paget's disease of bone

CXCL5/CXCR2 axis in tumor microenvironment as potential diagnostic biomarker and therapeutic target

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