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Anti-Cancer Activity of Verteporfin in Cholangiocarcinoma

  1. Author:
    Golino, Jihye L [ORCID]
    Wang, Xin [ORCID]
    Bian, Jing
    Ruf, Benjamin [ORCID]
    Kelly, Michael
    Karim,Baktiar
    Cam, Maggie C
    Xie, Changqing [ORCID]

  2. Author Address

    Thoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA., CCR Collaborative Bioinformatics Resource, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA., Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD 21701, USA., Molecular Histopathology Laboratory, Leidos Biomedical Research, Inc., Frederick, MD 21701, USA., Liver Cancer Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.,
    1. Year: 2023
    2. Date: Apr 25
    3. Epub Date: 2023 04 25
  2. Journal: Cancers
    1. 15
    2. 9
  4. Type of Article: Article
  1. Abstract:

    Cholangiocarcinoma (CCA) is a heterogenous malignancy that arises from the biliary epithelium and has a poor clinical prognosis. The Hippo/yes-associated protein (YAP) pathway has been reported to affect various aspects of tumorigenesis, with high expression of YAP1 being negatively associated with survival in CCA patients. Thus, we investigated the antitumoral effect of verteporfin, a YAP1 pathway inhibitor, in YAP1/AKT hydrodynamic tail vein injected murine models. We also used flow cytometry and single-cell RNA sequencing (scRNA-seq) to analyze the change in the immune cell profile and malignant cell stemness following verteporfin treatment. Our results demonstrated reduced liver weight and tumor formation in verteporfin-treated groups compared to that of a vehicle-treated group. Immune cell profiling through flow cytometry showed that relative to the vehicle, verteporfin induced a higher ratio of tumor-associated macrophage (TAM) M1/M2 and increased the percentage of activated CD8 T cell population (CD8+CD25+ and CD8+CD69+). scRNA-seq analysis showed significantly increased TAM M1 populations following verteporfin treatment and decreased proportions of stem-like cells within the malignant cell population. In summary, this study indicates that in CCA YAP/AKT murine models, verteporfin reduces tumorigenesis by polarizing anti-tumoral TAM and activating CD8 T cells and decreasing stem-like malignant cell proportions in the tumor microenvironment.

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External Sources

  1. View Full Text
  2. DOI: 10.3390/cancers15092454
  3. PMID: 37173920
  4. PMCID: PMC10177077
  5. PII : cancers15092454

Library Notes

  1. Fiscal Year: FY2022-2023
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