Serum Chemokine Ligand 5 (CCL5/RANTES) Level Might be Utilized as a Predictive Marker of Tumor Behavior and Disease Prognosis in Patients with Gastric Adenocarcinoma

Sima, Ali Reza; Sima, Hamid Reza; Rafatpanah, Houshang; Hosseinnezhad, Hanieh; Ghaffarzadehgan, Kamran; Valizadeh, Narges; Bahar, Mostafa Mehrabi; Hakimi, Hamid; Masoom, Anahita; Noorbakhsh, Amin; Satvati, Nahid Razavi; Raziee, Hamid

doi:10.1007/s12029-014-9652-5

Cited by 21 publications

(17 citation statements)

References 15 publications

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“…Moreover, CCL5 levels, as well as their changes in liquid biopsy samples, could potentially be useful to monitor or predict disease progress and treatment outcomes. Clinical evidence has revealed that elevated levels of tissue or plasma CCL5 are markers of an unfavorable outcome in patients with breast [ 41 , 42 , 43 , 44 ], cervical [ 45 ], prostate [ 26 ], ovarian [ 46 ], gastric [ 47 , 48 ], colorectal [ 49 ], or pancreatic cancer [ 50 ].…”

Section: Possible Clinical Applications: Ccl5 and Ccr5 As Therapeumentioning

confidence: 99%

“…While many virulence factors of H. pylori have been described, the CagA (cytotoxin-associated gene A) toxin, which is translocated into gastric epithelial cells via a bacterial secretion system, appears to be the most specific for the development of a pathological phenotype. Infection with H. pylori , a potent activator of NF-κB in gastric epithelial cells, increases CCL5 [ 47 , 81 , 82 , 83 ] and induces the expression of a variety of genes, including IL-1, IL-6, IL-8, IL-10, TNF-α, VEGF, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), cell cycle regulators, the matrix metalloproteinases (MMP)-2, MMP-7, MMP-9, and also adhesion molecules [ 82 , 84 ].…”

Section: Gastric Cancer and Its Tmementioning

confidence: 99%

“…Existing literature highlights the fundamental role of CCL5 in GC progression. GC patients have significantly higher serum CCL5 levels compared with control groups [ 47 , 98 ]. The overall survival of patients with CCL5 levels higher than 71 pg/mL was found to be significantly lower than that of patients with less CCL5 [ 47 , 99 ].…”

Section: The Ccl5/ccr5 Axis In Gc Development And/or Progressionmentioning

confidence: 99%

“…GC patients have significantly higher serum CCL5 levels compared with control groups [ 47 , 98 ]. The overall survival of patients with CCL5 levels higher than 71 pg/mL was found to be significantly lower than that of patients with less CCL5 [ 47 , 99 ]. Higher CCL5 levels were associated with lower histological differentiation, higher depth of tumor invasion, more frequent lymph nodes involvement, and advanced tumor stage [ 99 ].…”

Section: The Ccl5/ccr5 Axis In Gc Development And/or Progressionmentioning

confidence: 99%

“…Patients in the high CCL5 group also had stronger CCL5 immunohistochemistry (IHC) staining in tumor tissues [ 47 , 98 ] and in metastatic lymph nodes [ 101 ]. Thus, high CCL5 serum levels, along with strong IHC (CCL5) staining and poorly- or undifferentiated cancer, may be used to predict peritoneal dissemination and a poorer prognosis [ 100 ].…”

Section: The Ccl5/ccr5 Axis In Gc Development And/or Progressionmentioning

confidence: 99%

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Inhibition of the CCL5/CCR5 Axis against the Progression of Gastric Cancer

Aldinucci

Casagrande

2018

IJMS

109

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Despite the progress made in molecular and clinical research, patients with advanced-stage gastric cancer (GC) have a bad prognosis and very low survival rates. Furthermore, it is challenging to find the complex molecular mechanisms that are involved in the development of GC, its progression, and its resistance to therapy. The interactions of chemokines, also known as chemotactic cytokines, with their receptors regulate immune and inflammatory responses. However, updated research demonstrates that cancer cells subvert the normal chemokine role, transforming them into fundamental constituents of the tumor microenvironment (TME) with tumor-promoting effects. C-C chemokine ligand 5 (CCL5) is a chemotactic cytokine, and its expression and secretion are regulated in T cells. C-C chemokine receptor type 5 (CCR5) is expressed in T cells, macrophages, other leukocytes, and certain types of cancer cells. The interaction between CCL5 and CCR5 plays an active role in recruiting leukocytes into target sites. This review summarizes recent information on the role of the CCL5 chemokine and its receptor CCR5 in GC cell proliferation, metastasis formation, and in the building of an immunosuppressive TME. Moreover, it highlights the development of new therapeutic strategies to inhibit the CCL5/CCR5 axis in different ways and their possible clinical relevance in the treatment of GC.

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Section: Possible Clinical Applications: Ccl5 and Ccr5 As Therapeumentioning

confidence: 99%

Section: Gastric Cancer and Its Tmementioning

confidence: 99%

Section: The Ccl5/ccr5 Axis In Gc Development And/or Progressionmentioning

confidence: 99%

Section: The Ccl5/ccr5 Axis In Gc Development And/or Progressionmentioning

confidence: 99%

Section: The Ccl5/ccr5 Axis In Gc Development And/or Progressionmentioning

confidence: 99%

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Inhibition of the CCL5/CCR5 Axis against the Progression of Gastric Cancer

Aldinucci

Casagrande

2018

IJMS

109

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Loss of RUNX3 expression promotes cancer‐associated bone destruction by regulating CCL5, CCL19 and CXCL11 in non‐small cell lung cancer

Park

Lee

Kim

et al. 2015

The Journal of Pathology

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Non‐small cell lung cancer (NSCLC) frequently metastasizes to bone, which is associated with significant morbidity and a dismal prognosis. RUNX3 functions as a tumour suppressor in lung cancer and loss of expression occurs more frequently in invasive lung adenocarcinoma than in pre‐invasive lesions. Here, we show that RUNX3 and RUNX3‐regulated chemokines are linked to NSCLC‐mediated bone resorption. Notably, the receptor activator of nuclear factor‐κB ligand (RANKL)/osteoprotegerin (OPG) ratio, an index of osteoclastogenic stimulation, was significantly increased in human osteoblastic cells treated with conditioned media derived from RUNX3‐knockdown NSCLC cells. We aimed to identify RUNX3‐regulated factors that modify the osteoblastic RANKL/OPG ratio and found that RUNX3 knockdown led to CCL5 up‐regulation and down‐regulation of CCL19 and CXCL11 in NSCLC cells. Tumour size was noticeably increased and more severe osteolytic lesions were induced in the calvaria and tibiae of mice that received RUNX3‐knockdown cells. In response to RUNX3 knockdown, serum and tissue levels of CCL5 increased, whereas CCL19 and CXCL11 decreased. Furthermore, CCL5 increased the proliferation, migration, and invasion of lung cancer cells in a dose‐dependent manner; however, CCL19 and CXCL11 did not show any significant effects. The RANKL/OPG ratio in osteoblastic cells was increased by CCL5 but reduced by CCL19 and CXCL11. CCL5 promoted osteoclast differentiation, but CCL19 and CXCL11 reduced osteoclastogenesis in RANKL‐treated bone marrow macrophages. These findings suggest that RUNX3 and related chemokines are useful markers for the prediction and/or treatment of NSCLC‐induced bone destruction. © 2015 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

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