Discovery of YS-1 as a cell line of gastric inflammatory cancer-associated fibroblasts.

BACKGROUND: Inflammatory cancer-associated fibroblasts (iCAFs) was first identified by co-culture of pancreatic stellate cells and tumor organoids. The key feature of iCAFs is IL-6high/αSMAlow. We examine this phenomenon in gastric cancer using two cell lines of gastric fibroblasts (HGF and YS-1). METHODS AND RESULTS: HGF or YS-1 were co-cultured with MKN7 (a gastric adenocarcinoma cell line) in Matrigel. IL-6 protein levels in the culture supernatant were measured by ELISA. The increased production of IL-6 was not observed in any of the combinations. Instead, the supernatant of YS-1 exhibited the higher levels of IL-6. YS-1 showed IL-6high/αSMA (ACTA2)low in real-time PCR, mRNA-seq and immunohistochemistry. In mRNA-seq, iCAFs-associated genes and signaling pathways were up-regulated in YS-1. No transition to myofibroblastic phenotype was observed by monolayer culture, or the exposure to sonic hedgehog (SHH) or TGF-ß. YS-1 conditioned medium induced changes of morphology and stem-ness/differentiation in NUGC-3 (a human gastric adenocarcinoma cell line) and UBE6T-15 (a human bone marrow-derived mesenchymal stem cell line). CONCLUSIONS: YS-1 is a stable cell line of gastric iCAFs. This discovery will promote further research on iCAFs for many researchers.

The integration of bulk and single-cell sequencing data revealed the function of FKBP10 in the gastric cancer microenvironment.

Background: Due to the implementation of individualized treatment, the majority of gastric cancer patients have a favorable prognosis, but advanced gastric cancer with recurrence and distant metastasis still plagues some patients. As a member of the FK506-binding protein (FKBP65) family, there is growing evidence that FKBP10 plays a crucial role in tumorigenesis. However, the role of FKBP10 in the tumor microenvironment (TME) has been a prominent issue. Methods: The FKBP10 knockdown efficiency in gastric cancer cells was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Wound healing and transwell analysis were performed to detect variations in cell invasion and migration. We integrated single-cell and bulk sequencing data to further elaborate the impact of FKBP10 and FKBP10-coexpressed genes (FCGs) in the TME via a variety of bioinformatics approaches. Results: Here, we found that FKBP10 knockdown inhibited cell invasion and metastasis. FKBP10 was chiefly expressed in inflammatory cancer-associated fibroblasts (iCAFs), and FCGs principally mediated alterations in extracellular matrix (ECM) organization. Besides, according to nine prognosis-related FCGs, two disparate clusters were identified, and differences in tumor immune infiltration characteristics and immunotherapy response between different clusters were investigated. Conclusions: Our study provides insights into the expression and function of FKBP10 in the microenvironment of gastric cancer.