Division of General Thoracic Surgery, Department of Clinical Research, University Hospital Berne, Berne, Switzerland.
J Surg Oncol. 2010 Nov 1;102(6):689-98. doi: 10.1002/jso.21665.
Lung cancer is one of the leading causes of cancer-related deaths in the world. Although the origin still remains to be resolved, a prevailing hypothesis implies the involvement of cancer stem cells (CSCs) responsible for tumor initiation, maintenance, and progression. Embryonic stem cell marker, OCT4, encoding the spliced variants OCT4A and OCT4B, has recently been shown to have a dual role; as a potential adult stem cell marker and as a CSC marker in germline and somatic tumors.
We investigated the expression and intracellular distribution of OCT4A and OCT4B using flow cytometry, Western blot and quantitative RT-PCR analyses in normal and lung adenocarcinoma cell lines, primary cultures and tissue biopsies.
We demonstrate for the presence of rare OCT4A(+) and OCT4B(+) cells in normal lung. Notably, we observed higher levels of expression and atypical cytoplasmic distribution of OCT4A and not OCT4B, in the malignant setting, strongly indicating an oncogenic role in lung adenocarcinoma.
We postulate that OCT4A(+) cells are involved in the oncogenesis of lung adenocarcinoma. Identification of these cells and the biological processes vital for their subsistence, will guide the development of diagnostic and therapeutic clinical approaches with the goal of eliminating lung adenocarcinoma.
肺癌是全球癌症相关死亡的主要原因之一。尽管其起源仍有待解决，但一个流行的假设暗示了癌症干细胞（CSC）的参与，这些细胞负责肿瘤的起始、维持和进展。胚胎干细胞标志物 OCT4 编码剪接变体 OCT4A 和 OCT4B，最近被证明具有双重作用；既是潜在的成体干细胞标志物，也是生殖细胞和体细胞肿瘤中的 CSC 标志物。
我们使用流式细胞术、Western blot 和定量 RT-PCR 分析，研究了 OCT4A 和 OCT4B 在正常和肺腺癌细胞系、原代培养物和组织活检中的表达和细胞内分布。
我们证明了在正常肺中存在罕见的 OCT4A(+)和 OCT4B(+)细胞。值得注意的是，我们观察到在恶性环境中 OCT4A 的表达水平更高且存在非典型的细胞质分布，而不是 OCT4B，这强烈表明其在肺腺癌中具有致癌作用。
我们推测 OCT4A(+)细胞参与了肺腺癌的发生。鉴定这些细胞及其生存所需的生物学过程，将指导开发用于消除肺腺癌的诊断和治疗临床方法。
