Ameloblastoma cell lines derived from different subtypes demonstrate distinct developmental patterns in a novel animal experimental model

Objective: Ameloblastoma is a representative odontogenic tumor comprising several characteristic invasive forms, and its pathophysiology has not been sufficiently elucidated. A stable animal experimental model using immortalized cell lines is crucial to explain the factors causing differences among the subtypes of ameloblastoma, but this model has not yet been disclosed. In this study, a novel animal experimental model has been established, using immortalized human ameloblastoma-derived cell lines. Methodology: Ameloblastoma cells suspended in Matrigel were subcutaneously transplanted into the heads of immunodeficient mice. Two immortalized human ameloblastoma cell lines were used: AM-1 cells derived from the plexiform type and AM-3 cells derived from the follicular type. The tissues were evaluated histologically 30, 60, and 90 days after transplantation. Results: Tumor masses formed in all transplanted mice. In addition, the tumors formed in each group transplanted with different ameloblastoma cells were histologically distinct: the tumors in the group transplanted with AM-1 cells were similar to the plexiform type, and those in the group transplanted with AM-3-cells were similar to the follicular type. Conclusions: A novel, stable animal experimental model of ameloblastoma was established using two cell lines derived from different subtypes of the tumor. This model can help clarify its pathophysiology and hasten the development of new ameloblastoma treatment strategies

BTK isoforms p80 and p65 are expressed in head and neck squamous cell carcinoma (HNSCC) and involved in tumor progression

Here, we describe the expression of Bruton’s Tyrosine Kinase (BTK) in head and neck squamous cell carcinoma (HNSCC) cell lines as well as in primary HNSCC samples. BTK is a kinase initially thought to be expressed exclusively in cells of hematopoietic origin. Apart from the 77 kDa BTK isoform expressed in immune cells, particularly in B cells, we identified the 80 kDa and 65 kDa BTK isoforms in HNSCC, recently described as oncogenic. Importantly, we revealed that both isoforms are products of the same mRNA. By investigating the mechanism regulating oncogenic BTK-p80/p65 expression in HNSSC versus healthy or benign tissues, our data suggests that the epigenetic process of methylation might be responsible for the initiation of BTK-p80/p65 expression in HNSCC. Our findings demonstrate that chemical or genetic abrogation of BTK activity leads to inhibition of tumor progression in terms of proliferation and vascularization in vitro and in vivo. These observations were associated with cell cycle arrest and increased apoptosis and autophagy. Together, these data indicate BTK-p80 and BTK-p65 as novel HNSCC-associated oncogenes. Owing to the fact that abundant BTK expression is a characteristic feature of primary and metastatic HNSCC, targeting BTK activity appears as a promising therapeutic option for HNSCC patients

Lipoteichoic Acid and Lipopolysaccharides Are Affected by p38 and Inflammatory Markers and Modulate Their Promoting and Inhibitory Effects on Osteogenic Differentiation

Lipoteichoic acid (LTA) and lipopolysaccharide (LPS) are cell wall components of Gram-positive and Gram-negative bacteria, respectively. Notably, oral microflora consists of a variety of bacterial species, and osteomyelitis of the jaw caused by dental infection presents with symptoms of bone resorption and osteosclerosis. However, the effects of LTA and LPS on osteogenic differentiation have not yet been clarified. We examined the effects of LTA and LPS on osteoblasts and found that LTA alone promoted alizarin red staining at low concentrations and inhibited it at high concentrations. Additionally, gene expression of osteogenic markers (ALP, OCN, and OPG) were enhanced at low concentrations of LTA. High concentrations of LPS suppressed calcification potential, and the addition of low concentrations of LTA inhibited calcification suppression, restoring the gene expression levels of suppressed bone differentiation markers (ALP, BSP, and OCN). Moreover, the suppression of p38, a signaling pathway associated with bone differentiation, had opposing effects on gene-level expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), suggesting that mixed LTA and LPS infections have opposite effects on bone differentiation through concentration gradients, involving inflammatory markers (TNF-α and IL-6) and the p38 pathway