Cholangiocarcinoma Stem Cell

Cholangiocarcinoma (CCA), a malignancy with a dismal prognosis, is characterized by a high proportion of cancer stem cells (CSCs). Traditional methods for identifying CCA CSCs often fail to capture their dynamic nature. This study demonstrated a correlation between poor patient outcomes and the dual expression of SOX2/OCT4. Consequently, we established CCA cell lines harboring a live-cell CSC-specific reporter (SORE6) to track these cells. Analysis of five CCA cell lines revealed SORE6-positive (SORE6+) cells. These CCA CSC models were validated by assessing key CSC properties, including self-renewal, differentiation potential, and tumorigenicity. Furthermore, the reporter system, in conjunction with cell surface markers, allowed for the characterization of CCA CSC heterogeneity. Under standard CCA chemotherapies, the SORE6+ CSC population was enriched, likely due to intrinsic drug resistance and dedifferentiation capabilities. Importantly, treatment with CDK4/6 inhibitors was found to reduce the SORE6+ CCA cell population. These findings were further validated using advanced 3D culturing systems, including both 3D multi-spheroids and 3D multicellular spheroids, to more accurately mimic the tumor microenvironment. This study establishes diverse CSC models and elucidates drug-induced CSC plasticity in CCA through a live reporter system, offering novel insights and potential avenues for both clinical intervention and future research.

This project has yielded significant results, including the publication of an original research article (Kongtanawanich et al., 2024) and two additional manuscripts currently under review. Furthermore, the project’s findings have been presented at both international and national conferences, culminating in the Best Poster Presentation Award at the prestigious 42nd Thai Pharmacological and Therapeutic Society Conference (Kongtanawanich et al., 2021).