Ishikuro Masafumi, Sakamoto Kei, Kayamori Kou, Akashi Takumi, Kanda Hiroaki, Izumo Toshiyuki, Yamaguchi Akira
Section of Oral Pathology, Department of Oral Restitution, Graduate School of Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549 Japan.
Bone. 2008 Sep;43(3):621-7. doi: 10.1016/j.bone.2008.05.014. Epub 2008 May 28.
Gingival squamous cell carcinomas (SCCs) frequently invade the mandible or maxilla, and this invasion is associated with a worse prognosis. Although previous studies have suggested that bone destruction caused by gingival SCC is mediated by osteoclastic bone resorption rather than by tumor cells directly, the mechanism underlying the bone invasion remains poorly understood. We histopathologically investigated mandibular invasion patterns in 97 cases of primary gingival SCC and evaluated the correlations between bone invasion patterns and clinicopathological factors. Based on the histological examination of the mandibular invasion pattern, we classified the cases into 2 categories: expansive type and infiltrative type. Of the 97 cases, 52 were expansive type and 45, infiltrative type. Varying numbers of Howship's lacunae and osteoclasts were detected on the bone surface adjacent to the tumor cells. Compared to the expansive type, the infiltrative type showed increased numbers of osteoclasts at the interface of the tumor and the resorbing bone. Tumor cells showed no direct contact with osteoclasts and the adjacent bones, and in all cases varying amounts of fibrous connective tissues intervened between the tumor cells and the bone. The number of fibroblasts was significantly greater in the infiltrative type than in the expansive type. We also found a positive correlation between the number of osteoclasts and fibroblasts at the interface of the tumor and the resorbing bone. Immunohistochemistry revealed RANKL expression in the fibroblastic cells that were adjacent to the osteoclasts in the area of bone resorption. In coculture experiments, human gingival SCC cells (BHY) stimulated the expression of mouse RANKL mRNA in murine osteoblastic cells (MC3T3-E1). These results indicate that the fibrous stroma plays critical roles in osteoclastic bone resorption by gingival SCC through the RANKL-dependent pathways.
牙龈鳞状细胞癌（SCC）常侵犯下颌骨或上颌骨，这种侵犯与较差的预后相关。尽管先前的研究表明牙龈SCC引起的骨破坏是由破骨细胞介导的骨吸收，而非肿瘤细胞直接作用，但骨侵犯的潜在机制仍知之甚少。我们对97例原发性牙龈SCC的下颌骨侵犯模式进行了组织病理学研究，并评估了骨侵犯模式与临床病理因素之间的相关性。基于下颌骨侵犯模式的组织学检查，我们将病例分为两类：膨胀型和浸润型。97例病例中，52例为膨胀型，45例为浸润型。在肿瘤细胞相邻的骨表面检测到数量不等的豪希普陷窝和破骨细胞。与膨胀型相比，浸润型在肿瘤与吸收骨的界面处破骨细胞数量增加。肿瘤细胞与破骨细胞及相邻骨无直接接触，在所有病例中，肿瘤细胞与骨之间均有不同量的纤维结缔组织介入。浸润型中的成纤维细胞数量显著多于膨胀型。我们还发现肿瘤与吸收骨界面处的破骨细胞数量与成纤维细胞数量呈正相关。免疫组织化学显示，在骨吸收区域与破骨细胞相邻的成纤维细胞中表达核因子κB受体活化因子配体（RANKL）。在共培养实验中，人牙龈SCC细胞（BHY）刺激小鼠成骨细胞（MC3T3-E1）中鼠RANKL mRNA的表达。这些结果表明，纤维基质通过RANKL依赖途径在牙龈SCC破骨细胞介导的骨吸收中起关键作用。
