Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University, 374# Dianmian Avenue, Kunming, Yunnan 650101, China.
Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, China.
Dig Liver Dis. 2023 Aug;55(8):1114-1125. doi: 10.1016/j.dld.2022.12.007. Epub 2022 Dec 29.
Fibroblasts turn into cancer associated fibroblasts (CAFs) in the tumor microenvironment, which play an important role in tumor progression. However, the mechanism is unclear.
To investigate the role of CAFs with HS6ST1-overexpression in cell migration and invasion effects.
Human primary CAFs were isolated and identified from intrahepatic cholangiocarcinoma. mRNA profiles differences between CAFs and NFs were examined by using transcriptome sequencing. Using Transwell® migration assays, ICCA cells (RBE and HUCCT1) with NF-CM, CAF-CM, CAFs-CM, and CAFsST-CM were analyzed. Immunohistochemical staining were used to analyze the expression of HS6ST1 in CAF in 152 patients with ICCA. Overall survival (OS) was compared based on CAF HS6ST1 expression were analysed. The relationship between clinicopathological parameters and survival was also examined.
Successfully isolated CAFs is positive staining with αSMA, FSP-1, FAP, and PDGFR-β. Transcriptome sequencing showed that differently expressed genes were enriched in the function of the extracellular matrix and chemokine signaling pathway. HS6ST1 is differentially expressed between CAFs and NFs, and associated with the migration and invasion of ICCA cells. Moreover, HS6ST1 positive expression of CAFs predicted unfavorable prognosis in patients with intrahepatic cholangiocarcinoma and showed correlation with the presence of lymph node metastasis.
HS6ST1 is new possibilities for targeting the CAFs to reduce cholangiocarcinoma growth and metastasis.
成纤维细胞在肿瘤微环境中转化为癌相关成纤维细胞（CAFs），在肿瘤进展中发挥重要作用。然而，其机制尚不清楚。
研究过表达 HS6ST1 的 CAFs 在细胞迁移和侵袭中的作用。
从肝内胆管癌中分离和鉴定人原代 CAFs。采用转录组测序检测 CAFs 与 NF 之间的 mRNA 谱差异。使用 Transwell®迁移分析，分析 NF-CM、CAF-CM、CAFs-CM 和 CAFsST-CM 对 ICCA 细胞（RBE 和 HUCCT1）的迁移和侵袭作用。免疫组织化学染色分析 152 例 ICCA 患者中 CAF 中 HS6ST1 的表达。分析基于 CAF HS6ST1 表达的总生存期（OS）。还检查了临床病理参数与生存之间的关系。
成功分离的 CAFs 呈 αSMA、FSP-1、FAP 和 PDGFR-β 阳性染色。转录组测序显示，差异表达基因富集在细胞外基质和趋化因子信号通路的功能中。HS6ST1 在 CAFs 和 NF 之间差异表达，并与 ICCA 细胞的迁移和侵袭有关。此外，CAFs 中 HS6ST1 的阳性表达预测肝内胆管癌患者预后不良，并与淋巴结转移的存在相关。
HS6ST1 为靶向 CAFs 以减少胆管癌生长和转移提供了新的可能性。
