Department of Biochemistry and Genetics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan; Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.
Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.
Biochem Biophys Res Commun. 2014 Sep 5;451(4):491-6. doi: 10.1016/j.bbrc.2014.07.137. Epub 2014 Aug 11.
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.
成釉细胞瘤是一种发生在颌骨中的牙源性良性肿瘤，它侵犯骨骼并在局部复发。这种肿瘤通过广泛的手术切除来治疗，会导致各种问题，包括面部容貌的改变和咀嚼障碍。成釉细胞瘤有丰富的肿瘤基质，包括成纤维细胞和免疫细胞。虽然细胞间的相互作用被认为参与了许多疾病的发病机制，但成釉细胞瘤中的细胞间通讯尚未得到充分研究。在这项研究中，我们通过成釉细胞瘤中的可溶性因子研究了肿瘤细胞与基质成纤维细胞之间的相互作用。我们使用了人成釉细胞瘤细胞系（AM-3 成釉细胞瘤细胞）、人成纤维细胞（HFF-2 成纤维细胞）和原代培养的人成釉细胞瘤组织成纤维细胞，并分析了成釉细胞瘤相关的细胞间通讯对基因表达、细胞因子分泌、细胞迁移和增殖的影响。AM-3 成釉细胞瘤细胞分泌的白细胞介素（IL）-1α水平高于 HFF-2 成纤维细胞。用 AM-3 成釉细胞瘤细胞的条件培养基处理可上调 HFF-2 成纤维细胞和原代培养的成釉细胞瘤组织成纤维细胞中 IL-6 和 IL-8 的基因表达和分泌。用 AM-3 细胞预先用抗 IL-1α 抗体和 IL-1 受体拮抗剂处理可中和 AM3 刺激的成纤维细胞中 IL-6 和 IL-8 的产生。相反，HFF-2 成纤维细胞以 IL-6 和 IL-8 依赖的方式刺激 AM-3 成釉细胞瘤细胞的迁移。总之，成釉细胞瘤细胞和成纤维细胞通过这些细胞因子相互作用，形成一个微环境，导致成釉细胞瘤的扩展。
