Emori Makoto, Tsukahara Tomohide, Murase Masaki, Kano Masanobu, Murata Kenji, Takahashi Akari, Kubo Terufumi, Asanuma Hiroko, Yasuda Kazuyo, Kochin Vitaly, Kaya Mitsunori, Nagoya Satoshi, Nishio Jun, Iwasaki Hiroshi, Sonoda Tomoko, Hasegawa Tadashi, Torigoe Toshihiko, Wada Takuro, Yamashita Toshihiko, Sato Noriyuki
Department of Orthopedic Surgery, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan ; Department of Pathology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan.
Department of Pathology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan.
PLoS One. 2013 Dec 20;8(12):e84187. doi: 10.1371/journal.pone.0084187. eCollection 2013.
Epithelioid sarcoma (ES) is a relatively rare, highly malignant soft tissue sarcoma. The mainstay of treatment is resection or amputation. Currently other therapeutic options available for this disease are limited. Therefore, a novel therapeutic option needs to be developed. In the present study, we established a new human ES cell line (ESX) and analyzed the characteristics of its cancer stem-like cells/cancer-initiating cells (CSCs/CICs) based on ALDH1 activity. We demonstrated that a subpopulation of ESX cells with high ALDH1 activity (ALDH(high) cells) correlated with enhanced clonogenic ability, sphere-formation ability, and invasiveness in vitro and showed higher tumorigenicity in vivo. Next, using gene expression profiling, we identified CD109, a GPI-anchored protein upregulated in the ALDH(high) cells. CD109 mRNA was highly expressed in various sarcoma cell lines, but weakly expressed in normal adult tissues. CD109-positive cells in ESX predominantly formed spheres in culture, whereas siCD109 reduced ALDH1 expression and inhibited the cell proliferation in vitro. Subsequently, we evaluated the expression of CD109 protein in 80 clinical specimens of soft tissue sarcoma. We found a strong correlation between CD109 protein expression and the prognosis (P = 0.009). In conclusion, CD109 might be a CSC/CIC marker in epithelioid sarcoma. Moreover, CD109 is a promising prognostic biomarker and a molecular target of cancer therapy for sarcomas including ES.
上皮样肉瘤（ES）是一种相对罕见的高度恶性软组织肉瘤。治疗的主要方法是切除或截肢。目前针对这种疾病的其他治疗选择有限。因此，需要开发一种新的治疗选择。在本研究中，我们建立了一种新的人ES细胞系（ESX），并基于乙醛脱氢酶1（ALDH1）活性分析了其癌症干细胞样细胞/肿瘤起始细胞（CSCs/CICs）的特征。我们证明，具有高ALDH1活性的ESX细胞亚群（ALDH（高）细胞）与体外增强的克隆形成能力、成球能力和侵袭性相关，并且在体内表现出更高的致瘤性。接下来，通过基因表达谱分析，我们鉴定出CD109，一种在ALDH（高）细胞中上调的糖基磷脂酰肌醇（GPI）锚定蛋白。CD109 mRNA在各种肉瘤细胞系中高表达，但在正常成人组织中弱表达。ESX中的CD109阳性细胞在培养中主要形成球体，而siCD109降低了ALDH1表达并抑制了体外细胞增殖。随后，我们评估了80例软组织肉瘤临床标本中CD109蛋白的表达。我们发现CD109蛋白表达与预后之间存在强相关性（P = 0.009）。总之，CD109可能是上皮样肉瘤中的一种CSC/CIC标志物。此外，CD109是一种有前景的预后生物标志物，也是包括ES在内的肉瘤癌症治疗的分子靶点。
Zotero 插件
