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

Abstract

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-␤)

Arrayed molecular barcoding identifies TNFSF13 as a positive regulator of acute myeloid leukemia-initiating cells

“…In agreement with previous studies showing that TNFSF13 is expressed by infiltrating neutrophils in solid tumors 39,40 and by myeloid BM cells in multiple myeloma, 41,42 we found that TNFSF13 was secreted by CD11b + Gr-1 + myeloid cells but not by the corresponding murine AML cells. This finding suggests that mature myeloid BM cells support AML cells by secreting TNFSF13.…”

Heterogeneity Among Neutrophils

“…Pro-neoplastic properties of the N2 phenotype cells are associated with the production of proangiogenic and growth factors (e.g., VEGF: vascular endothelial growth factor), as well as enzymes degrading the extracellular matrix (e.g., MMP-9: matrix metalloproteinase 9). It is also believed that TANs/N2 are capable of inhibiting the immune response against cancer cells by influencing the activity of other cells (Jabłońska et al 2012 ; Schmielau and Finn 2001 ; Tazawa et al 2003 ).…”

Neutrophils and oral squamous cell carcinoma: lessons learned and future directions

“…Studies Cancer biomarker Neutrophil infiltration [26] OSCC [27] OSCC-tongue NLR [28] HNSCC [29] HNSCC [30] OSCC Neutrophil-secreted proteins [31] OSCC [32] OSCC-tongue [33] OSCC [34] OSCC [35] OSCC [36] OSCC [37] OSCC ROS [38] Review [39] OSCC [40] OSCC Cancer microenvironment MMPs [41] HNSCC [42] HNSCC [43] Fibrosarcoma [44] Cervical Angiogenesis [45] Fibrosarcoma [46] Pancreatic ductal adenocarcinoma [47] Fibrosarcoma Prostate NETs [48] Lung [22] Liver Microbiome, neutrophils, and cancer [49] OSCC [50] OSCC [51] OSCC-gingival [52] Colorectal [53] HNSCC [54] HNSCC Modulation of cell function and signaling [55] Orohypopharingeal [56] HNSCC [57] HNSCC [58] Multiple tumors [26] OSCC [59] Chronic myelogenous leukemia…”

“…Members of the TNF superfamily of secreted proteins, including APRIL [35], TRAIL, and DR5 [36], were also investigated as possible oral cancer biomarkers. APRIL has been shown to regulate tumor cell survival and proliferation through binding to heparin sulfate side-chains of proteoglycans or to the calcium modulator and cyclophilin ligand interactor [65].…”