Takeda Daisuke, Hasegawa Takumi, Ueha Takeshi, Iwata Eiji, Harada Risa, Sakakibara Akiko, Kawamoto Teruya, Minamikawa Tsutomu, Sakai Yoshitada, Komori Takahide
Departments of Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
Departments of Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
Anticancer Res. 2017 Mar;37(3):1075-1082. doi: 10.21873/anticanres.11419.
BACKGROUND/AIM: Cancer stem cells are suspected to contribute to malignancy in tumors. Hypoxia affects cell differentiation and induces stem-cell-like characteristics in malignancies. Induced pluripotency was demonstrated in mouse fibroblasts by reprogramming with four transcriptional factors: Oct3/4, Sox2, c-Myc, and Klf4. Conversely, oncogenic transformations frequently express transcriptional factors and Nanog. Therefore, cancer cells present some similarities with induced pluripotent stem (iPS) cells.
We investigated the expression of iPS-related genes in vitro and in clinical samples to identify their relationships with hypoxia and tumorigenesis.
Oral squamous cell carcinoma (SCC) cells were used to show that expression levels of Oct3/4, Sox2, and Nanog were significantly increased in hypoxic condition in vitro and in moderately- and poorly-differentiated samples.
We propose that Oct3/4, Sox2 and Nanog are associated with tumor hypoxia characterized in oral SCC and that these factors may also contribute to the undifferentiated potency observed in oral SCC clinically.
背景/目的:癌症干细胞被怀疑在肿瘤恶性化过程中起作用。缺氧会影响细胞分化并在恶性肿瘤中诱导出干细胞样特征。通过用四种转录因子(Oct3/4、Sox2、c-Myc和Klf4)进行重编程,在小鼠成纤维细胞中证明了诱导多能性。相反,致癌转化经常表达转录因子和Nanog。因此,癌细胞与诱导多能干细胞(iPS细胞)存在一些相似之处。
我们在体外和临床样本中研究了iPS相关基因的表达,以确定它们与缺氧和肿瘤发生的关系。
使用口腔鳞状细胞癌(SCC)细胞表明,在体外缺氧条件下以及在中分化和低分化样本中,Oct3/4、Sox2和Nanog的表达水平显著增加。
我们提出Oct3/4、Sox2和Nanog与口腔SCC中特征性的肿瘤缺氧有关,并且这些因子也可能导致临床上在口腔SCC中观察到的未分化潜能。