Related Experiment Video
Updated: Mar 17, 2026
Generation of Induced Pluripotent Stem Cells from Human Melanoma Tumor-infiltrating Lymphocytes
Published on: November 11, 2016
Induction of artificial cancer stem cells from tongue cancer cells by defined reprogramming factors
Koji Harada1, Tarannum Ferdous2, Dan Cui3
1Department of Oral and Maxillofacial Surgery, Yamaguchi University Graduate School of Medicine, 1-1-1, Minamikogushi, Ube, 755-8505, Japan. harako@yamaguchi-u.ac.jp.
Background:
The cancer stem cells (CSCs), a small subpopulation of cells in tumor are responsible for the tumor initiation, growth, recurrence and metastasis of cancer, as well as resistance of cancers to drugs or radiotherapy. CSCs are an important target for the development of novel strategies in cancer treatment. However, CSCs-targeted new anti-cancer drug discovery is currently hindered by the lack of easy and reliable methods for isolating, collecting and maintaining sufficient number of CSCs. Here, we examined whether introduction of defined reprogramming factors (Oct4, shp53, Sox2, Klf4, l-Myc and Lin28) into HSC2 tongue cancer cells could transform the HSC2 into HSC2 with CSCs properties.
Methods:
We introduced the defined reprogramming factors into HSC2 tongue cancer cells via episomal vectors by electroporation method to generate transfectant cells. We investigated the malignant properties of the transfectant cells by cell proliferation assay, migration assay, wound healing assay, sphere formation assay, chemosensitivity and radiosensitivity assay in vitro; and also examined the tumorigenic potential of the transfectants in vivo.
Results:
The transfectant cells (HSC2/hOCT3/4-shp53-F, HSC2/hSK, HSC2/hUL, HSC2/hOCT3/4-shp53-F + hSK, HSC2/hOCT3/4-shp53-F + hUL, HSC2/hSK + hUL, HSC2/hOCT3/4-shp53-F + hSK + hUL) displayed a malignant phenotype in culture and form tumors on the back of nude mice more efficiently than parental HSC2 and control HSC2/EGFP transfectant cells. They exhibited increased resistance to chemotherapeutic agents; 5-fluorouracil, cisplatin, docetaxel, trifluorothymidine, zoledronic acid, cetuximab, bortezomib and radiation when compared with HSC2 and HSC2/EGFP. Among all the transfected cells, HSC2/hOCT3/4-shp53-F + hSK + hUL cell containing all of the reprogramming factors showed the most aggressive and malignant properties and presented the highest number of spheres in the culture medium containing human recombinant fibroblast Growth Factor-2 (FGF-2) and epidermal Growth Factor (EGF).
Conclusion:
These findings suggest that artificial cancer stem cells obtained by the induction of cellular reprogramming may be useful for investigating the acquisition of potential malignancy as well as screening the CSCs-targeting drugs.
Insights
Reprogramming tongue cancer cells created artificial cancer stem cells (CSCs) with enhanced malignancy and drug resistance. These CSCs show promise for cancer research and drug screening.
Area of Science:
- Oncology
- Stem Cell Biology
- Cancer Research
Background:
- Cancer stem cells (CSCs) drive tumor growth, metastasis, and treatment resistance.
- Targeting CSCs is crucial for novel cancer therapies.
- Current limitations in CSC isolation hinder drug discovery.
Purpose of the Study:
- To investigate if defined reprogramming factors can induce CSC properties in HSC2 tongue cancer cells.
- To establish a model for studying CSCs and screening CSC-targeting drugs.
Main Methods:
- Defined reprogramming factors (Oct4, shp53, Sox2, Klf4, l-Myc, Lin28) were introduced into HSC2 cells via episomal vectors.
- Transfected cells were analyzed for malignant properties in vitro (proliferation, migration, sphere formation, drug/radiation sensitivity) and in vivo (tumorigenicity).
Main Results:
- Transfected cells exhibited enhanced malignant phenotypes, increased tumorigenicity in vivo, and greater resistance to multiple chemotherapeutic agents and radiation.
- The combination of all reprogramming factors (HSC2/hOCT3/4-shp53-F+hSK+hUL) resulted in the most aggressive properties and highest sphere formation.
Conclusions:
- Artificial CSCs can be generated through cellular reprogramming.
- These induced CSCs serve as a valuable model for investigating cancer malignancy and for screening CSC-targeting drugs.
More Related Videos
08:15Fabrication of Tongue Extracellular Matrix and Reconstitution of Tongue Squamous Cell Carcinoma In Vitro
Published on: June 20, 2018
05:45In Vitro Establishment of a Genetically Engineered Murine Head and Neck Cancer Cell Line using an Adeno-Associated Virus-Cas9 System
Published on: January 9, 2020
Related Concept Videos
02:40Cancer Stem Cells and Tumor Maintenance
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
01:29Somatic to iPS Cell Reprogramming
01:06Induced Pluripotent Stem Cells
Somatic...
01:13Induced Pluripotent Stem Cells
01:24Methods of Nuclear Reprogramming
01:21Stem Cell Therapy for Tissue Regeneration
Types of Stem Cells used in Stem Cell Therapy
The two main cell...