Department of Molecular Cytogenetics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
Cancer Sci. 2018 Nov;109(11):3623-3633. doi: 10.1111/cas.13783. Epub 2018 Sep 21.
Distant metastasis to liver, lung, brain, or bone occurs by circulating tumor cells (CTC). We hypothesized that a subset of CTC had features that are more malignant than tumor cells at the primary site. We established a highly malignant cell line, Panc-1-CTC, derived from the human pancreatic cancer cell line Panc-1 using an in vivo selection method. Panc-1-CTC cells showed greater migratory and invasive abilities than its parent cell line in vitro. In addition, Panc-1-CTC cells had a higher tumor-forming ability than parent cells in vivo. To examine whether a difference in malignant phenotypes exists between Panc-1-CTC cells and parent cells, we carried out comprehensive gene expression array analysis. As a result, Panc-1-CTC significantly expressed transforming growth factor beta-induced (TGFBI), an extracellular matrix protein, more abundantly than did parent cells. TGFBI is considered to regulate cell adhesion, but its functions remain unclear. In the present study, knockdown of TGFBI reduced cell migration and invasion abilities, whereas overexpression of TGFBI increased both abilities. Moreover, elevated expression of TGFBI was associated with poor prognosis in patients with pancreatic cancer.
循环肿瘤细胞（CTC）可转移至肝、肺、脑或骨。我们假设 CTC 的一个亚群具有比原发性肿瘤细胞更恶性的特征。我们使用体内选择方法从人胰腺癌细胞系 Panc-1 中建立了一个高度恶性的细胞系 Panc-1-CTC。与亲本细胞系相比，Panc-1-CTC 细胞在体外具有更强的迁移和侵袭能力。此外，Panc-1-CTC 细胞在体内比亲本细胞具有更高的成瘤能力。为了检查 Panc-1-CTC 细胞与亲本细胞之间是否存在恶性表型的差异，我们进行了全面的基因表达谱分析。结果表明，Panc-1-CTC 细胞比亲本细胞更大量地表达转化生长因子β诱导（TGFBI），一种细胞外基质蛋白。TGFBI 被认为调节细胞黏附，但它的功能尚不清楚。在本研究中，TGFBI 的敲低降低了细胞迁移和侵袭能力，而过表达 TGFBI 则增加了这两种能力。此外，TGFBI 的高表达与胰腺癌患者的预后不良相关。
