Identification and Isolation of Cancer Stem Cells: from Biomarker Discovery to Setting Up Therapeutic Strategies
Chemo-resistance is a major problem in cancer therapy as aggressive cancer cells develop mechanisms to counteract chemotherapeutic drugs. Cancer Stem Cells (CSCs) are considered at the origin of cancer relapse and recurrence in cancer patients and following chemotherapy. Like their stem cell counterparts, CSCs possess the stemness properties of self-renewal and to generate differentiated cells that contribute to tumour heterogeneity. Although several CSCs biomarkers have been identified, the specificity of their expression remains a concern. Therefore, the identification of specific CSCs biomarkers and associated cellular pathways, for targeted cancer therapies, is a major challenge facing scientists and clinicians working in this moving field. Using a NANOG-EGFP lentiviral expression system, we isolated from cancer cell lines, a population of CSCs that are able to self-renew and differentiate, and that have high tumourigenic capacity when tested in NOD SCID xenograft mouse model. Biomarkers discovery approaches using mass spectrometry, microarrays and miRNome analyses enabled the identification of several proteins, mRNAs and miRNAs that are specifically expressed by this polulation of CSCs. Selected biomarkers are being investigated for potential use in patients clinical evaluation (Diagnosis and prognosis) using tissue microarrays from cancer patients and for the development of anti-cancerous therapeutic strategies.