HS6ST1 overexpressed in cancer-associated fibroblast and inhibited cholangiocarcinoma progression.

Backgroud: Fibroblasts turn into cancer associated fibroblasts (CAFs) in the tumor microenvironment, which play an important role in tumor progression. However, the mechanism is unclear.

Aims: To investigate the role of CAFs with HS6ST1-overexpression in cell migration and invasion effects.

Methods: 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.

Results: 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.

Conclusion: HS6ST1 is new possibilities for targeting the CAFs to reduce cholangiocarcinoma growth and metastasis.