Department of Molecular Medicine, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy.
Department of Radiology, Oncology and Pathology, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy.
Int J Mol Sci. 2024 Feb 1;25(3):1782. doi: 10.3390/ijms25031782.
In intrahepatic cholangiocarcinoma (iCCA), thrombospondin 1 (THBS1) and 2 (THBS2) are soluble mediators released in the tumor microenvironment (TME) that contribute to the metastatic spreading of iCCA cells via a lymphatic network by the trans-differentiation of vascular endothelial cells to a lymphatic-like phenotype. To study the direct role of THBS1 and THBS2 on the iCCA cells, well-established epithelial (HuCCT-1) and mesenchymal (CCLP1) iCCA cell lines were subjected to recombinant human THBS1 and THBS2 (rhTHBS1, rhTHBS2) for cellular function assays. Cell growth, cell adhesion, migration, and invasion were all enhanced in both CCLP1 and HuCCT-1 cells by the treatment with either rhTHBS1 or rhTHBS2, although they showed some variability in their intensity of speeding up cellular processes. rhTHBS2 was more intense in inducing invasiveness and in committing the HuCCT-1 cells to a mesenchymal-like phenotype and was therefore a stronger enhancer of the malignant behavior of iCCA cells compared to rhTHBS1. Our data extend the role of THBS1 and THBS2, which are not only able to hinder the vascular network and promote tumor-associated lymphangiogenesis but also exacerbate the malignant behavior of the iCCA cells.
在肝内胆管癌（iCCA）中，血小板反应蛋白 1（THBS1）和 2（THBS2）是在肿瘤微环境（TME）中释放的可溶性介质，通过血管内皮细胞向淋巴样表型的转分化，促进 iCCA 细胞通过淋巴网络进行转移扩散。为了研究 THBS1 和 THBS2 对 iCCA 细胞的直接作用，我们使用了两种已建立的上皮（HuCCT-1）和间充质（CCLP1）iCCA 细胞系，用重组人 THBS1 和 THBS2（rhTHBS1、rhTHBS2）进行细胞功能测定。用 rhTHBS1 或 rhTHBS2 处理后，两种细胞系的细胞生长、细胞黏附、迁移和侵袭能力均增强，尽管它们在加速细胞进程的强度上存在一些差异。rhTHBS2 在诱导侵袭和使 HuCCT-1 细胞向间充质样表型转化方面更为强烈，因此与 rhTHBS1 相比，它更能增强 iCCA 细胞的恶性行为。我们的数据扩展了 THBS1 和 THBS2 的作用，它们不仅能够阻碍血管网络并促进肿瘤相关淋巴管生成，而且还会加剧 iCCA 细胞的恶性行为。
