Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, Thailand.
Department of Pathology, Faculty of Medicine, Khon Kaen University, and the Liver Fluke and Cholangiocarcinoma Research Center, Khon Kaen University, Khon Kaen, Thailand.
Cell Adh Migr. 2021 Dec;15(1):152-165. doi: 10.1080/19336918.2021.1924422.
Extensive desmoplasia in cholangiocarcinoma (CCA) is associated with tumor aggressiveness, indicating a need for further understanding of CCA cell-matrix interaction. This study demonstrated laminin as the most potent attractant for CCA cell migration and the vast elevation of its receptor integrin β4 (ITGB4) in CCA cell lines. Besides, their high expressions in CCA tissues were correlated with lymphatic invasion and the presence of ITGB4 was also associated with short survival time. ITGB4 silencing revealed it as the receptor for laminin-induced HuCCA-1 migration, but KKU-213 utilized 37/67-kDa laminin receptor (LAMR) instead. These findings highlight the role of ITGB4 and LAMR in transducing laminin induction of CCA cell migration and the potential of ITGB4 as diagnostic and prognostic biomarkers for CCA.
在胆管癌（CCA）中广泛的细胞外基质增生与肿瘤侵袭性相关，这表明需要进一步了解 CCA 细胞与细胞外基质的相互作用。本研究表明层粘连蛋白是 CCA 细胞迁移最有效的趋化因子，并且在 CCA 细胞系中其受体整合素 β4（ITGB4）的含量大量增加。此外，它们在 CCA 组织中的高表达与淋巴浸润相关，并且 ITGB4 的存在也与较短的生存时间相关。ITGB4 沉默表明其是层粘连蛋白诱导 HuCCA-1 迁移的受体，但 KKU-213 利用 37/67-kDa 层粘连蛋白受体（LAMR）代替。这些发现强调了 ITGB4 和 LAMR 在转导层粘连蛋白诱导的 CCA 细胞迁移中的作用，以及 ITGB4 作为 CCA 诊断和预后生物标志物的潜力。
