HepG2 cells acquire stem cell-like characteristics after immune cell stimulation

Area of Science:

• Immunology
• Cancer Biology
• Stem Cell Research

Background:

• Cancer stem cells (CSCs) drive tumor formation and treatment failure.
• Chronic inflammation is linked to CSCs, but the exact mechanism is unclear.
• This study investigates how immune cell interactions influence CSC phenotype acquisition.

Purpose of the Study:

• To examine the relationship between immune cell stimulation and the development of CSC-like properties in cancer cells.
• To understand how B lymphocytes and macrophages affect cancer cell stemness.

Main Methods:

• HepG2 hepatocarcinoma cells were treated with mouse splenic B cells (MSBCs) and mouse peritoneal macrophage cells (MPMCs).
• Stem cell characteristics were assessed via biomarker assays, in vitro/in vivo tumoroid and colony formation assays, and signal transduction pathway analysis.
• Gene and protein expression of stemness markers (EpCAM, ALDH, CD133, CD44) were analyzed using RT-PCR and FACS.

Main Results:

• MSBC-HepG2 and MPMC-HepG2 cells exhibited enhanced stemness: self-renewal, proliferation, chemoresistance, and tumorigenicity.
• These cells overexpressed CSC markers (EpCAM, ALDH, CD133, CD44) compared to parental HepG2 cells.
• Tumor formation in NOD/SCID mice and activation of Notch and SHH pathways were observed in treated cells.

Conclusions:

• Immune cells can paradoxically promote CSC characteristics.
• B lymphocytes and macrophages may contribute to cancer stemness, influencing tumor development and therapeutic outcomes.
• The immune system exhibits a dual role in cancer, potentially fostering CSCs despite anti-tumor functions.