Murata Shin-Ichi, Warigaya Kenji, Matsuzaki Ibu, Itonaga Masahiro, Shimizu Yuki, Shuto Masayo
Department of Human Pathology, Wakayama Medical University, 811-1 Kimiidera, Wakayama, 641-8509, Japan,
Virchows Arch. 2015 Jun;466(6):625-35. doi: 10.1007/s00428-015-1744-5. Epub 2015 Mar 6.
Nuclear polarity is characterized by intracytoplasmic nuclear positioning and alignment in the tissue. The mechanisms responsible for maintaining nuclear polarity in normal cells and its disturbance in neoplastic cells are not understood. We studied microtubule-organizing center (MTOC) positioning-mediated nuclear polarity in various normal and neoplastic human tissues, as well as in cultured cells. To visualize the MTOC in cells, gamma-tubulin and pericentrin were immunohistochemically stained by fluorescence and non-fluorescence methods. Position of MTOC in normal and neoplastic tissue was assessed by spatial relationship with nucleus and apico-basal axis. We found MTOC positioning to be related to morphogenesis in various normal and neoplastic human tissues, as well as in cultured cells. MTOC positions were different between two-dimensional cultured isolated cells and three-dimensional cultured gland-formed cells. The MTOC position was specific depending on the cell type in the tissue structure. In particular, glandular and urothelial epithelium had a strong relationship with preservation of nuclear polarity and MTOC positioning. Carcinoma cells showed an irregular position or absence of the MTOC depending on poorer differentiation and higher grade of carcinomas. In conclusion, the position of the MTOC affects regulation of nuclear polarity and morphogenesis of normal and pathological tissue structure.
核极性的特征是细胞核在细胞质内的定位以及在组织中的排列。维持正常细胞中核极性及其在肿瘤细胞中受到干扰的机制尚不清楚。我们研究了微管组织中心(MTOC)定位介导的各种正常和肿瘤性人类组织以及培养细胞中的核极性。为了在细胞中可视化MTOC,通过荧光和非荧光方法对γ-微管蛋白和中心粒外周蛋白进行免疫组织化学染色。通过与细胞核和顶-基轴的空间关系评估MTOC在正常和肿瘤组织中的位置。我们发现MTOC定位与各种正常和肿瘤性人类组织以及培养细胞中的形态发生有关。二维培养的分离细胞和三维培养的腺形成细胞之间的MTOC位置不同。MTOC位置取决于组织结构中的细胞类型。特别是,腺上皮和尿路上皮与核极性的维持和MTOC定位有密切关系。癌细胞根据分化较差和肿瘤分级较高而表现出MTOC位置不规则或缺失。总之,MTOC的位置影响核极性的调节以及正常和病理组织结构的形态发生。