Cassidy Linda, Choi Meerim, Meyer Jason, Chang Rui, Seigel Gail M
Center for Hearing and Deafness, University at Buffalo, 3435 Main Street, Cary 137 Buffalo, NY 14214, USA.
Indiana University, Department of Biology, Indianapolis, IN 46202, USA.
J Biomark. 2013;2013:960862. doi: 10.1155/2013/960862. Epub 2013 May 27.
Pluripotent stem cell markers can be useful for diagnostic evaluation of human tumors. The novel pluripotent marker stage-specific embryonic antigen-5 (SSEA-5) is expressed in undifferentiated human induced pluripotent cells (iPSCs), but little is known about SSEA-5 expression in other primitive tissues (e.g., human tumors). We evaluated SSEA-5 immunoreactivity patterns in human tumors, cell lines, teratomas, and iPS cells together with another pluripotent cell surface marker L1 cell adhesion molecule (L1CAM). We tested two hypotheses: (1) SSEA-5 and L1CAM would be immunoreactive and colocalized in human tumors; (2) SSEA-5 and L1CAM immunoreactivity would persist in iPSCs following retinal differentiating treatment. SSEA-5 immunofluorescence was most pronounced in primitive tumors, such as embryonal carcinoma. In tumor cell lines, SSEA-5 was highly immunoreactive in Capan-1 cells, while L1CAM was highly immunoreactive in U87MG cells. SSEA-5 and L1CAM showed colocalization in undifferentiated iPSCs, with immunopositive iPSCs remaining after 20 days of retinal differentiating treatment. This is the first demonstration of SSEA-5 immunoreactivity in human tumors and the first indication of SSEA-5 and L1CAM colocalization. SSEA-5 and L1CAM warrant further investigation as potentially useful tumor markers for histological evaluation or as markers to monitor the presence of undifferentiated cells in iPSC populations prior to therapeutic use.
多能干细胞标志物可用于人类肿瘤的诊断评估。新型多能标志物阶段特异性胚胎抗原-5(SSEA-5)在未分化的人类诱导多能细胞(iPSC)中表达,但关于SSEA-5在其他原始组织(如人类肿瘤)中的表达情况知之甚少。我们评估了SSEA-5在人类肿瘤、细胞系、畸胎瘤和iPS细胞中的免疫反应模式,同时评估了另一种多能细胞表面标志物L1细胞粘附分子(L1CAM)。我们测试了两个假设:(1)SSEA-5和L1CAM在人类肿瘤中具有免疫反应性且共定位;(2)视网膜分化处理后,SSEA-5和L1CAM免疫反应性在iPSC中持续存在。SSEA-5免疫荧光在原始肿瘤如胚胎癌中最为明显。在肿瘤细胞系中,SSEA-5在Capan-1细胞中具有高度免疫反应性,而L1CAM在U87MG细胞中具有高度免疫反应性。SSEA-5和L1CAM在未分化的iPSC中共定位,视网膜分化处理20天后仍有免疫阳性的iPSC。这是SSEA-5在人类肿瘤中的首次免疫反应性证明,也是SSEA-5和L1CAM共定位的首次迹象。SSEA-5和L1CAM作为潜在有用的肿瘤标志物用于组织学评估,或作为在治疗前监测iPSC群体中未分化细胞存在的标志物,值得进一步研究。