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Objectives: Various types of cells comprising a complex and diverse cell population are required for the biological activities of odontogenic keratocyst (OKC). Immune and non‐immune cells collaborate via cytokine‐ or chemokine‐mediated communication and direct cell–cell interactions. This study aimed to characterize the immune ecosystem and understand the potential chemotactic role of OKC fibroblasts in immune cell migration. Materials and Methods: Mass cytometry of 41 markers was employed for the classification of OKC cells from six OKC samples. Immunofluorescence staining and single‐cell RNA sequencing (GSE176351) were used for the detection of fibroblast subpopulations. Enzyme‐linked immunosorbent assay and immunofluorescence staining were employed for chemokine detection in hypoxia‐ and/or HIF‐1α inhibitor‐treated OKC fibroblasts and tissues. Chemotaxis assay was employed to determine the chemotactic effect of fibroblasts via co‐culture with peripheral blood mononuclear cells. A cell communication network was constructed based on the single‐cell RNA sequencing data. Results: The characterization of the immune cell types of OKC evidenced the enrichment of macrophages, neutrophils and B cells. The majority (41.5%) of fibroblast subsets consisted of chemokine ligand‐enriched myofibroblasts. The activation of the HIF‐1α signaling pathway in fibroblasts was associated with chemokine release. The chemokines released by OKC fibroblasts remarkably promoted the migration of peripheral blood mononuclear cells in the co‐culture system. Close interactions between myofibroblasts and immune cells were validated by cell–cell interaction analysis. Increased RANKL expression was detected in OKC fibroblasts in the co‐culture system with peripheral blood mononuclear cells. Conclusions: Our results provided deep insights into the immune ecosystem and highlighted the potential chemotactic effects of chemokine‐enriched myofibroblasts within OKCs. The close interaction between immune cells and fibroblasts demonstrated in this study may be responsible for the osteoclastogenic effects of OKC fibroblasts. [ABSTRACT FROM AUTHOR]

The article presents the discussion on exploring more valuable diagnostic and prognostic methods for improving the long-term survival of OSCC patients. Topics include OSCC treatment modalities increasing patients' survival mainly include surgery, chemotherapy, radiation therapy, and adjuvant treatment; and CD8+ T cell-derived extracellular vesicles significantly destroying the tumor stroma.

Bone resorption in the jaws is one of the most severe complications of keratocystic odontogenic tumors (KCOTs), and can be treated by either enucleation or marsupialization. However, the effects of marsupialization on bone regeneration adjacent to KCOTs, and the mechanisms involved, are still unclear. In this study, samples of 27 KCOTs were collected (20 before marsupialization and 7 after marsupialization) to detect the expression of bone regeneration-related molecules adjacent to KCOTs by immunohistochemistry and real-time quantitative polymerase chain reaction (qPCR). The results showed that bone formation was significantly enhanced in the KCOT capsule wall adjacent to bone after marsupialization, as demonstrated by alkaline phosphatase activity assay and immunostaining for bone morphogenetic protein. Moreover, immunohistochemistry revealed that osteoprotegerin (OPG) was up-regulated in the KCOT capsule wall adjacent to bone after marsupialization, while receptor activator of nuclear factor-κB ligand (RANKL) was down-regulated. Real-time qPCR also demonstrated increased expression of OPG after marsupialization, accompanied by a decrease in the expression of osteoclastogenesis-related molecules such as cathepsin K, matrix metalloproteinase-9, NFATc1, RANK and RANKL. This study provides further evidence that marsupialization may promote bone regeneration adjacent to KCOTs partially through regulation of the OPG/RANK/RANKL signaling pathway. [ABSTRACT FROM AUTHOR]

Objectives Methods Results Conclusions This study aimed to investigate the expression and biological significance of Semenogelin 1 (SEMG1), a member of the cancer‐testis antigen family, in oral squamous cell carcinoma (OSCC). Further, we explored its potential association with metabolism‐related molecules.SEMG1 expression levels in OSCC were determined through immunohistochemistry, flow cytometry, and Western blot analyses. To decipher the biological implications of SEMG1 in OSCC, the CAL27 OSCC cell line was either stably overexpressed with SEMG1 or subjected to SEMG1‐shRNA knockdown. The relationship between clinicopathological parameters and SEMG1 expression in OSCC patients was also assessed.SEMG1 was found to be overexpressed in OSCC, though its expression was not influenced by the pathological grade. The fluorescent dihydroethidium assay indicated that SEMG1 augmented reactive oxygen species production. The mitochondrial membrane potential assay suggested a significant upregulation of mitochondrial membrane potential by SEMG1. Cell cycle assessments highlighted that SEMG1 overexpression led to a notable rise in cells entering the S‐phase. Additionally, a strong correlation between SEMG1 expression and both ENO1 and PKM2 expression in OSCC was observed.The findings underscore the elevated expression of SEMG1 in OSCC and its contributory role in the tumorigenesis of OSCC patients. [ABSTRACT FROM AUTHOR]

Objectives: Ameloblastoma (AM), a locally aggressive tumor with extensive growth capacity, causes significant damage to the jaw and affects facial appearance. Although the high prevalence of BRAF V600E mutation in AM is known, its specific impacts on patients with AM remain unclear. Thus, the present study investigated the role of BRAF V600E mutation, thereby focusing on its impact on AM invasion and growth., Materials and Methods: Immunohistochemical analysis was used to compare BRAF V600E, MMP2, MMP9, and Ki-67 expressions in AM (n = 49), normal oral mucosa (NOM) (n = 10), and odontogenic keratocyst (OKC) (n = 15) tissues. AM was further classified according to the presence or absence of BRAF V600E. The relationship between BRAF V600E and invasion as well as growth was evaluated. In addition, correlation analysis was performed using immunohistochemistry and confirmed via double-labeling immunofluorescence. Finally, comparative analyses using mass spectrometry, immunohistochemistry, and immunofluorescence were performed to explore and identify underlying mechanisms., Results: AM exhibited a higher incidence of BRAF V600E mutation than NOM and OKC. BRAF V600E expression was positively correlated with the invasion-associated proteins MMP2 and MMP9 and the growth-related protein Ki-67. Proteomic data revealed that BRAF V600E primarily activates the MAPK signaling pathway in AM, particularly driving the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2)., Conclusions: In summary, the findings suggested that the BRAF V600E mutation enhances the invasion and growth abilities of AM via the MAPK/ERK signaling pathway. Thus, targeting BRAF V600E or the MAPK/ERK pathway may be a potential AM therapy., (© 2024 Wiley Periodicals LLC.)