Isolation and phenotypic characterization of cancer stem cells from metastatic oral cancer cells

Iara Gonçalves Aquino ¹, Florence Juana Maria Cuadra-Zelaya ², Ana Laura Valença Bizeli ¹

¹Departamento de Diagnóstico Oral, Faculdade de Odontologia de Piracicaba, Universidade Estadual de Campinas (UNICAMP), Piracicaba, São Paulo, Brazil.
²Department of Pathology, School of Dentistry, University of El Salvador, San Salvador, El Salvador.
³Regional Blood Center of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
⁴Departamento de Patologia, Faculdade de Ciências Médicas, Universidade Estadual de Campinas (UNICAMP), Campinas, São Paulo, Brazil.
⁵Cancer and Translational Medicine Research Unit, Faculty of Medicine and Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland.
⁶Department of Oral and Maxillofacial Diseases, Helsinki University Central Hospital, and Translational Immunology Research Program (TRIMM), University of Helsinki, Helsinki, Finland.
⁷HUSLAB, Department of Pathology, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland.
⁸Programa de Pós-Graduação Em Biologia Buco-Dental, Faculdade de Odontologia de Piracicaba, Universidade Estadual de Campinas (UNICAMP), Piracicaba, São Paulo, Brazil.
⁹Faculdade de Medicina São Leopoldo Mandic, Campinas, São Paulo, Brazil.

⁰Departamento de Diagnóstico Oral, Faculdade de Odontologia de Piracicaba, Universidade Estadual de Campinas (UNICAMP), Piracicaba, São Paulo, Brazil.

Oral Diseases +

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May 20, 2024

View abstract on PubMed

Summary

Researchers isolated cancer stem cell (CSC) subpopulations from oral squamous cell carcinoma (OSCC) and found they possess enhanced in vitro and in vivo cancer capabilities, suggesting potential therapeutic targets.

Area Of Science

Oncology
Cancer Stem Cell Biology
Oral Squamous Cell Carcinoma Research

Background

Oral squamous cell carcinoma (OSCC) is a significant global health concern.
Cancer stem cells (CSCs) are implicated in tumor initiation, metastasis, and therapeutic resistance.
Understanding CSC heterogeneity is crucial for developing effective OSCC treatments.

Purpose Of The Study

To isolate and characterize distinct cancer stem cell (CSC) subpopulations from a metastatic OSCC cell line.
To investigate the in vitro and in vivo phenotypic properties of these CSC subpopulations.
To identify CSC characteristics that contribute to OSCC progression and metastasis.

Main Methods

Isolation of CSC subpopulations (CSC-M1, CSC-E, CSC-M2) from OSCC cell line LN-1A using Fluorescence-Activated Cell Sorting (FACS) based on CD44 and CD326 expression.
In vitro analysis of proliferation, clonogenic potential, adhesion, migration, and epithelial-mesenchymal transition (EMT) markers.
In vivo assessment of tumor formation and metastasis through subcutaneous and orthotopic inoculation in BALB/c mice.

Main Results

Distinct CSC subpopulations exhibited differential expression of EMT markers (E-cadherin, vimentin, Slug).
CSC-M1 and CSC-M2 subpopulations demonstrated enhanced proliferation, colony formation, and extracellular matrix adhesion in vitro.
CSC-E and CSC-M2 subpopulations formed larger tumors and showed increased metastatic potential in vivo.

Conclusions

The isolated CSC subpopulations exhibit heightened in vitro cancer capabilities and in vivo tumorigenic and metastatic potential.
These findings highlight the heterogeneity of CSCs in OSCC and their contribution to disease progression.
The characterized CSC subpopulations represent promising targets for novel therapeutic strategies against OSCC.

Keywords:

CD326 CD44 cancer stem cells epithelial‐mesenchymal transition oral squamous cell carcinoma

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