Sathi Gulsan Ara, Tamamura Ryo, Tsujigiwa Hidetsugu, Katase Naoki, Lefeuvre Mathieu, Siar Chong Huat, Matsuda Hiroyuki, Nagatsuka Hitoshi
Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan;
Exp Ther Med. 2012 Mar;3(3):397-402. doi: 10.3892/etm.2011.437. Epub 2011 Dec 28.
Recent studies have established that, in benign tumors, a large number of cancer stem cells are present, which have great implications in tumor development. However, in ameloblastoma, a highly aggressive, locally invasive tumor with a high recurrence rate, whether or not cancer stem-like cells are present remains undetermined. Therefore, in this study we analyzed the protein expression of three candidate stem cell markers in ameloblastoma. Immunohistochemical staining for cancer stem cell (CSC) markers (CD133, CD44 and ABCG2) and for the proliferation marker Ki-67 was performed using 23 ameloblastoma cases. In all 23 samples, CD133, CD44 and ABCG2 were expressed. Nine (39.13%) cases showed high expression and 14 cases (60.87%) showed low expression for CD133. Twelve of the 23 cases (52.17%) showed high expression and 11 cases (47.83%) showed low expression for both CD44 and ABCG2, respectively. Ki-67 was mainly expressed in peripheral ameloblast-like cells, suggesting that these cells have a higher degree of differentiation and, therefore, are less likely to contain cancer stem-like cells. On the other hand, cells positive for CSC markers situated at the close proximity to peripheral cells were devoid of Ki-67 and may have the potential to be cancer stem-like cells. After analyzing the correlation between expression of three CSC markers with clinicopathological factors and Ki-67 expression, only CD44 expression was correlated with tumor recurrence (P=0.0391). In conclusion, this study showed various expression patterns of different types of cancer stem cell markers and the presence of candidate CSC-like cells in ameloblastoma, which are possibly involved in cell proliferation, tumor progression and recurrence.
最近的研究表明，在良性肿瘤中存在大量癌症干细胞，这对肿瘤发展具有重要意义。然而，在成釉细胞瘤（一种具有高度侵袭性、局部浸润性且复发率高的肿瘤）中，是否存在癌症干细胞样细胞仍未确定。因此，在本研究中，我们分析了成釉细胞瘤中三种候选干细胞标志物的蛋白表达情况。使用23例成釉细胞瘤病例进行了癌症干细胞（CSC）标志物（CD133、CD44和ABCG2）以及增殖标志物Ki-67的免疫组织化学染色。在所有23个样本中，CD133、CD44和ABCG2均有表达。9例（39.13%）病例CD133呈高表达，14例（60.87%）呈低表达。23例病例中有12例（52.17%）CD44呈高表达，11例（47.83%）呈低表达；23例病例中有12例（52.17%）ABCG2呈高表达，11例（47.83%）呈低表达。Ki-67主要表达于外周成釉细胞样细胞，提示这些细胞分化程度较高，因此含有癌症干细胞样细胞的可能性较小。另一方面，位于外周细胞附近的CSC标志物阳性细胞缺乏Ki-67，可能具有成为癌症干细胞样细胞的潜力。在分析三种CSC标志物的表达与临床病理因素及Ki-67表达之间的相关性后，仅CD44表达与肿瘤复发相关（P = 0.0391）。总之，本研究显示了不同类型癌症干细胞标志物在成釉细胞瘤中的多种表达模式以及候选CSC样细胞的存在，这些细胞可能参与细胞增殖、肿瘤进展和复发。
