title: 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-β 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-β 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.
authors.affiliation: Department of Immunology, Medical University of Bialystok, Poland. ewa.jablonska@umb.edu.pl
authors.forename: Ewa
authors.initials: E
authors.lastname: Jabłońska
authors.forename: Natalia
authors.initials: N
authors.lastname: Wawrusiewicz-Kurylonek
authors.forename: Marzena
authors.initials: M
authors.lastname: Garley
authors.forename: Wioletta
authors.initials: W
authors.lastname: Ratajczak-Wrona
authors.forename: Bożena
authors.initials: B
authors.lastname: Antonowicz
authors.forename: Dorota
authors.initials: D
authors.lastname: Dziemiańczyk-Pakieła
authors.forename: Jakub
authors.initials: J
authors.lastname: Jabłoński
authors.forename: Adam
authors.initials: A
authors.lastname: Krętowski
authors.forename: Stanisława Zyta
authors.initials: SZ
authors.lastname: Grabowska
mesh_terms: D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009504:Neutrophils / Q000201:enzymology / Q000378:metabolism*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000097:blood; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000097:blood / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; C495345:TLR4 protein, human; C114631:TNFSF13 protein, human; D051197:Toll-Like Receptor 4; D016212:Transforming Growth Factor beta; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D048049:Extracellular Signal-Regulated MAP Kinases