Cells with stemness features are generated from in vitro transformed human fibroblasts

Area of Science:

• Oncology
• Cell Biology
• Cancer Research

Background:

• Cancer stem cells (CSCs) are implicated in tumor maintenance, progression, and relapse.
• The precise origin of CSCs remains an area of active investigation.

Purpose of the Study:

• To investigate if transformed human somatic cells can acquire CSC properties.
• To characterize CSC-like cells derived from in vitro transformed fibroblasts.

Main Methods:

• Utilized in vitro transformed human fibroblasts (cen3tel cells) and the tumorsphere assay.
• Analyzed self-renewal capacity, Sox2 overexpression, gene expression profiles, and tumorigenicity in NSG mice.

Main Results:

• Transformed fibroblasts formed spheres with self-renewal capacity and Sox2 overexpression, indicating CSC-like features.
• Sphere cells showed deregulation of a c-MYC/miR-34a circuitry and transcriptional reprogramming, including pathways related to tumorigenesis and stemness.
• Both sphere cells and adherent cells were tumorigenic in mice, though sphere cells engrafted more rapidly.

Conclusions:

• Human somatic cells can acquire CSC properties during transformation, highlighting tumor cell plasticity.
• The CSC phenotype and tumorigenicity can be uncoupled, as non-CSC-like cells also exhibit tumorigenic potential.