interleukin-8 and Ameloblastoma

The objective of the present study was twofold: first, to assess aspirates for use in cytokine profiling and second, to initiate pilot analyses to determine whether the cytokine profiling can serve as an aid in the diagnosis of jaw lesions.. The aspirates from 12 benign odontogenic cysts and tumors of the jaw were collected and randomized, and a formal incisional biopsy was performed to establish the tissue diagnosis. The biopsies revealed keratocystic odontogenic tumor, ameloblastoma, and dentigerous cyst. The cystic aspirate was analyzed using the Q-Plex Human Cytokine Screen to detect cytokine expression and determine the level of expression for each pathologic entity. An array of 16 cytokines was investigated, including interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, IL-15, IL-17, IL-23, interferon-γ, tumor necrosis factor (TNF)-α, and TNF-β. Tables were developed to determine the ratio of expression for the candidate cytokine pairs that were differentially expressed among the 3 pathologic entities encountered. One-way analysis of variance was used to search for significant differences in the ratio of expression of the candidate pairs among the 3 entities.. Cytokines expressed by the 3 distinct jaw lesions were detected in the aspirate without the need for tissue biopsy. Cytokine profiling of these entities is possible owing to differential expression of the various cytokines studied. The ratio of expression was significant (P < .05) for 15 pairs of cytokines: IL-5/IL-1α, IL-4/IL-2, IL-8/IL-4, TNF-β/IL-6, IL-23/IL-6, TNF-α/IL-23, TNF-α/TNF-β, TNF-α/IL-8, TNF-β/IL-5, TNF-β/TNF-α, TNF-β/IL-13, IL-12/IL-23, IL-13/IL-15, IL-15/IL-2, and IL-6/IL-2. A comparison of the mean values indicated a "high/low" expression value for each lesion type for the 15 cytokine pairs.. Cytokines, expressed by the 3 groups of jaw lesions, can be detected in the cystic aspirate, and a comparison of the ratio of the expression of the aspirates demonstrated a differential expression pattern of cytokines among the 3 groups. These ratios could assist in establishing a prompt and accurate diagnosis of lesions that might be difficult to discern clinically and radiographically. The use of a simple, minimally invasive aspiration procedure can help to establish an accurate diagnosis.

Topics: Adolescent; Adult; Ameloblastoma; Child; Cross-Sectional Studies; Cyst Fluid; Cytokines; Dentigerous Cyst; Female; Humans; Interferon-gamma; Interleukin-10; Interleukin-12; Interleukin-13; Interleukin-15; Interleukin-17; Interleukin-1alpha; Interleukin-1beta; Interleukin-23; Interleukin-4; Interleukin-5; Interleukin-8; Jaw Neoplasms; Lymphotoxin-alpha; Male; Middle Aged; Odontogenic Tumors; Protein Array Analysis; Tumor Necrosis Factor-alpha; Young Adult

Epithelial-mesenchymal transition (EMT) is important in the tooth development and tumor invasion. We investigated the effect of interleukin-8 (IL-8) on the EMT process in primary-cultured ameloblastoma tumor cells (AM-P) and ameloblastoma immortalized tumor cells (AM-L) and its underlying mechanism.. IL-8 levels in ameloblastomas were detected by immunofluorescence staining and ELISA. AM-P cells and AM-L cells were stimulated with IL-8, and EMT transcription factors, total β-catenin and phosphorylated-β-catenin (p-β-catenin) levels were determined by Western blot analysis and immunofluorescence staining. β-catenin siRNA was used to knockdown β-catenin expression in AM-P cells and AM-L cells stimulated with IL-8.. IL-8 was highly expressed in the solid ameloblastomas. IL-8 promoted the EMT process in ameloblastoma tumor cells in vitro, as evidenced by decreased E-cadherin and increased vimentin, twist and zeb1 levels. IL-8 also increased total β-catenin and p-β-catenin expression in ameloblastoma tumor cells, and β-catenin knockdown partially inhibited the EMT process in tumor cells, as evidenced by increased E-cadherin, and decreased vimentin and zeb1 levels.. IL-8 could promote EMT in ameloblastoma tumor cells by activating β-catenin and its downstream transcription factor zeb1.

Topics: Ameloblastoma; beta Catenin; Cadherins; Cell Line, Tumor; Epithelial-Mesenchymal Transition; Gene Expression Regulation, Neoplastic; Humans; Interleukin-8

Ameloblastoma is a common odontogenic benign tumor located in the jaws and is characterized by severe local bone destruction. The current study aimed to investigate the effect of interactions between tumor cells and bone marrow stromal cells (BMSCs) on osteoclast formation in ameloblastoma. The impact of ameloblastoma/BMSC interactions on cytokine production, gene expression and osteoclastogenesis was examined using an immortalized ameloblastoma cell line that the authors' previously established. The results demonstrated that interactions between ameloblastoma cells and BMSCs increased interleukin (IL)‑8 and activin A secretion by BMSCs. IL‑8 expression in BMSCs was modulated by tumor‑derived tumor necrosis factor‑α and IL‑8 contributed to osteoclast formation not only directly but also by stimulating receptor activator of NF‑κB ligand (RANKL) expression in BMSCs. Activin A secretion in BMSCs was stimulated by ameloblastoma cells via cell‑to‑cell‑mediated activation of c‑Jun N‑terminal kinase activation, acting as a cofactor of RANKL to induce osteoclast formation and function. The present study highlights the critical role of communication between BMSCs and ameloblastoma cells in bone resorption in ameloblastoma.

Topics: Activins; Adult; Ameloblastoma; Cells, Cultured; Female; Gene Expression Regulation, Neoplastic; Humans; Interleukin-8; Jaw Neoplasms; Male; Mesenchymal Stem Cells; Osteoclasts; Osteolysis; Tumor Cells, Cultured; Up-Regulation; Young Adult

Ameloblastoma is an odontogenic benign tumor that occurs in the jawbone, which invades bone and reoccurs locally. This tumor is treated by wide surgical excision and causes various problems, including changes in facial countenance and mastication disorders. Ameloblastomas have abundant tumor stroma, including fibroblasts and immune cells. Although cell-to-cell interactions are considered to be involved in the pathogenesis of many diseases, intercellular communications in ameloblastoma have not been fully investigated. In this study, we examined interactions between tumor cells and stromal fibroblasts via soluble factors in ameloblastoma. We used a human ameloblastoma cell line (AM-3 ameloblastoma cells), human fibroblasts (HFF-2 fibroblasts), and primary-cultured fibroblasts from human ameloblastoma tissues, and analyzed the effect of ameloblastoma-associated cell-to-cell communications on gene expression, cytokine secretion, cellular motility and proliferation. AM-3 ameloblastoma cells secreted higher levels of interleukin (IL)-1α than HFF-2 fibroblasts. Treatment with conditioned medium from AM-3 ameloblastoma cells upregulated gene expression and secretion of IL-6 and IL-8 of HFF-2 fibroblasts and primary-cultured fibroblast cells from ameloblastoma tissues. The AM3-stimulated production of IL-6 and IL-8 in fibroblasts was neutralized by pretreatment of AM-3 cells with anti-IL-1α antibody and IL-1 receptor antagonist. Reciprocally, cellular motility of AM-3 ameloblastoma cells was stimulated by HFF-2 fibroblasts in IL-6 and IL-8 dependent manner. In conclusion, ameloblastoma cells and stromal fibroblasts behave interactively via these cytokines to create a microenvironment that leads to the extension of ameloblastomas.

Topics: Ameloblastoma; Cell Communication; Cell Line, Tumor; Humans; Interleukin-1alpha; Interleukin-6; Interleukin-8; Jaw Neoplasms; Receptors, Interleukin-1; Stromal Cells