Mal'tseva D V, Makarova Yu A, Raigorodskaya M P, Rodin S A
BioClinicum Research Center, Moscow, Russia.
P. A. Hertsen Moscow Oncology Research Center, Affiliated Department of Center of Radiology, the Ministry of Health of Russia, Obninsk, Russia.
Bull Exp Biol Med. 2019 Jan;166(3):377-382. doi: 10.1007/s10517-019-04354-x. Epub 2019 Jan 9.
The effects of laminins 332 and 411 (LM-332 and LM-411) on the epithelial-mesenchymal transformation of colorectal cancer cells (lines HT-29, HCT-116, and RKO) with different metastatic potential were studied. Culturing of RKO cells on both laminins was associated with modification of the cell shape, which became more spindle-like or stellate, and with higher expression of EMT-associated transcription factors SNAI1 and ZEB1. In addition, culturing on LM-332 led to a decrease in the expression of laminin α5 chain (LAMA5), while culturing on LM-411 led to an increase in the expression of a cell-cell junction component (DSP). Culturing of HT-29 cells on LM-332 was associated with the formation of more close contacts between the cells and by a higher expression of epithelial markers (CDH1 and DSP genes) and a decrease in SNAI1 expression. Culturing of HCT-116 cells on both laminins led to a decrease in FN1 expression, on LM-332 - to an increase in laminin α4 chain (LAMA4) expression, and on LM-411 - to a lesser expression of LAMA4 and transcription factors SNAI2 and ZEB1. These data indicated that colorectal cancer cell adhesion to laminins contributed to the probability of epithelial-mesenchymal transformation of cells. The direction of this transformation seemed to depend on the initial characteristics of the cells.
研究了层粘连蛋白332和411（LM - 332和LM - 411）对具有不同转移潜能的结肠癌细胞（HT - 29、HCT - 116和RKO细胞系）上皮 - 间质转化的影响。RKO细胞在这两种层粘连蛋白上培养均与细胞形态改变有关，细胞变得更呈纺锤形或星状，且上皮 - 间质转化相关转录因子SNAI1和ZEB1的表达更高。此外，在LM - 332上培养导致层粘连蛋白α5链（LAMA5）表达降低，而在LM - 411上培养导致细胞间连接成分（DSP）表达增加。HT - 29细胞在LM - 332上培养与细胞间形成更紧密接触有关，且上皮标志物（CDH1和DSP基因）表达更高，SNAI1表达降低。HCT - 116细胞在这两种层粘连蛋白上培养均导致FN1表达降低，在LM - 332上培养导致层粘连蛋白α4链（LAMA4）表达增加，在LM - 411上培养导致LAMA4以及转录因子SNAI2和ZEB1表达降低。这些数据表明结肠癌细胞与层粘连蛋白的黏附有助于细胞上皮 - 间质转化的可能性。这种转化的方向似乎取决于细胞的初始特征。
