TLR4 ligation induces expression of APRIL molecule in human neutrophils — a preliminary study

Jabłońska, Ewa; Wawrusiewicz‐Kurylonek, Natalia; Garley, Marzena; Krętowski, Adam

doi:10.5603/fhc.2012.0029

Cited by 5 publications

(2 citation statements)

References 31 publications

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“…Our previous observations also indicated the involvement of TLR4 ligation by LPS in the induction of the APRIL molecule in human peripheral blood neutrophils. Furthermore, our results suggest that LPS encourages neutrophils to express APRIL through the ERK1/2 signaling pathway [21]. Among the endogenous factors, an important role in the biology of neutrophils is played by transforming growth factor ␤ (TGF-␤), which seems to be a major, proximal cytokine within tumors that defines the tumor-associated neutrophils (TAN) phenotype and skews differentiation toward the "N2" protumorigenic phenotype.…”

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confidence: 82%

A proliferation-inducing ligand (APRIL) in neutrophils of patients with oral cavity squamous cell carcinoma

Jabłońska

Wawrusiewicz‐Kurylonek²,

Garley³

et al. 2012

European Cytokine Network

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Available data indicating a role for neutrophils in the tumor-host reactions are controversial. In 37 patients with oral cavity squamous cell carcinoma (OSCC), we investigated the expression of a tumor-promoting, proliferation-inducing ligand (APRIL) molecule by peripheral blood neutrophils isolated from blood samples collected at presentation and three weeks after surgery, and the serum levels of TGF-␤ in the same samples. Additionally, we investigated the consequences of TLR4 activation by LPS for the synthesis of APRIL by those cells.The levels of mRNA for APRIL and TLR4 were measured using a real-time PCR method. Western blot analysis was used to assay the expressions of APRIL and ERK1/2 in cell lysates. The results of the present study revealed the unfavorable features of the detection, in the blood, of neutrophils displaying an enhanced expression of the tumor-promoting APRIL molecule. The increased expression and release of APRIL accompanying advanced stages of disease demonstrated by these cells, combined with the increased number of neutrophils, may be an important marker of disease progression in the patient group examined. Simultaneously, an increased level of circulating TGF-␤ in the serum of these patients appeared to be associated with the overexpression of APRIL in their neutrophils. In contrast to the healthy controls, TLR4 expression and the ERK1/2 signaling pathway appear to play only minor roles in APRIL induction in the cells of patients with cancer. The changes presented in the current study suggest that modulation of the expression of tumor-promoting APRIL, in addition to TRAIL and BAFF, might be taken into account in the development of new strategies for supportive immunotherapy of OSCC disease and possibly for other types of neoplasm as well.Key words: oral cavity squamous cell carcinoma (OCSCC), a proliferation-inducing ligand (APRIL), polymorphonuclear neutrophils (PMNs), Toll-like receptor 4 (TLR4), the extracellular signal-regulated kinases 1/2 (ERK1/2), transforming growth factor ␤ (TGF-␤)

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confidence: 82%

A proliferation-inducing ligand (APRIL) in neutrophils of patients with oral cavity squamous cell carcinoma

Jabłońska

Wawrusiewicz‐Kurylonek²,

Garley³

et al. 2012

European Cytokine Network

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“…HS activates TLR4 in dendritic cells, causing enhanced cell maturation and alloreactive T-cell responses 34 , and lipopolysaccharide (LPS), a TLR4-specific bacterial ligand, increases APRIL expression in Caco-2 intestinal epithelial cells 35 . In neutrophils treated with LPS, TLR4 expression positively correlates with APRIL expression 36 , and this was suggested to play a part in the TLR4-mediated host immune response. Here, we examined the possibility that TLR4 is involved in BCC HS-induced neutrophil APRIL secretion.…”

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confidence: 99%

Neutrophil TLR4 and PKR are targets of breast cancer cell glycosaminoglycans and effectors of glycosaminoglycan-induced APRIL secretion

et al. 2018

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A proliferation-inducing ligand (APRIL), which induces survival and migration signals and tumor growth, is commonly observed in breast cancer tissues but is not often expressed in breast cancer cells themselves. Here, we examined whether breast cancer cells induce APRIL secretion from neutrophils, which are frequently recruited into the breast tumor microenvironment. We found that breast cancer cells do stimulate neutrophils to secrete APRIL through their glycosaminoglycans. Breast cancer cells depleted of heparan sulfate or chondroitin sulfate glycosaminoglycans lose their ability to induce APRIL secretion from neutrophils, and heparan sulfate and chondroitin sulfate can induce secretion that is comparable to that of breast cancer cell-induced secretion. While stimulation of the RNA-activated protein kinase (PKR) is sufficient to induce neutrophil APRIL secretion, both PKR and the toll-like receptor 4 (TLR4) are required for breast cancer cell glycosaminoglycan-induced secretion as separate and specific inhibition of TLR4 or PKR completely prevents the process, suggesting that breast cancer cell glycosaminoglycans target neutrophil TLR4 and PKR to trigger APRIL secretion. Thus, apart from the putative role of cell surface heparan sulfate in binding APRIL that leads to cell growth, we demonstrate that heparan sulfate, as well as chondroitin sulfate plays a novel role in promoting neutrophil secretion of APRIL that could lead to further cell growth. We propose that breast cancer cells take advantage of the neutrophil recruitment to the tumor microenvironment through the dual role of heparan sulfate as cell surface receptor or docking molecule for APRIL and as a ligand that induces neutrophil APRIL secretion to promote their own growth.

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The up-regulation expression of APRIL is a marker of glottic malignant disease

Lian

Fang

Han

et al. 2013

Eur Arch Otorhinolaryngol

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A proliferation-inducing ligand (APRIL) is a member of the tumor necrosis factor (TNF) family. Recent studies have implied that APRIL is closely related to solid tumors and hematological tumors, indicating that APRIL could be a potential marker to diagnose glottic malignant disease. The purpose of this study was to investigate the difference of the APRIL mRNA and protein expression in glottic malignant disease, corresponding adjacent non-neoplastic tissues and glottic benign lesion, and detect the influence of different clinical parameter in glottic carcinoma. The APRIL mRNA expression in the glottic carcinoma, corresponding adjacent non-neoplastic tissues and glottic polypus tissue samples from patients was detected by qRT-PCR. Moreover, we studied the APRIL protein expression in pathological sections of other patients with glottic carcinoma or glottic polypus using immunohistochemistry. All the patients with different clinical parameter underwent surgery. Using qRT-PCR, we revealed an up-regulation of APRIL mRNA expression in glottic carcinoma as compared to glottic polypus and corresponding adjacent non-neoplastic tissues, but no significant difference with T stages, histopathological differentiation grade or lymph node metastasis in glottic carcinoma. The result of the immunohistochemistry was the same, with no influence of different clinical parameter in glottic carcinoma. These results strongly suggest that APRIL could be a potential diagnosed marker to distinguish glottic malignant disease from glottic benign lesion, and it may play an important role in the development of glottic malignant disease.

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TLR4 ligation induces expression of APRIL molecule in human neutrophils — a preliminary study

Cited by 5 publications

References 31 publications

A proliferation-inducing ligand (APRIL) in neutrophils of patients with oral cavity squamous cell carcinoma

A proliferation-inducing ligand (APRIL) in neutrophils of patients with oral cavity squamous cell carcinoma

Neutrophil TLR4 and PKR are targets of breast cancer cell glycosaminoglycans and effectors of glycosaminoglycan-induced APRIL secretion

The up-regulation expression of APRIL is a marker of glottic malignant disease

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