Abstract
Cancer stem cells are responsible for tumor progression, metastasis, therapy resistance and cancer recurrence, doing their identification and isolation of special relevance. Here we show that low adherent breast and colon cancer cells subpopulations have stem-like properties. Our results demonstrate that trypsin-sensitive (TS) breast and colon cancer cells subpopulations show increased ALDH activity, higher ability to exclude Hoechst 33342, enlarged proportion of cells with a cancer stem-like cell phenotype and are enriched in sphere- and colony-forming cells in vitro. Further studies in MDA-MB-231 breast cancer cells reveal that TS subpopulation expresses higher levels of SLUG, SNAIL, VIMENTIN and N-CADHERIN while show a lack of expression of E-CADHERIN and CLAUDIN, being this profile characteristic of the epithelial-to-mesenchymal transition (EMT). The TS subpopulation shows CXCL10, BMI-1 and OCT4 upregulation, differing also in the expression of several miRNAs involved in EMT and/or cell self-renewal such as miR-34a-5p, miR-34c-5p, miR-21-5p, miR-93-5p and miR-100-5p. Furthermore, in vivo studies in immunocompromised mice demonstrate that MDA-MB-231 TS cells form more and bigger xenograft tumors with shorter latency and have higher metastatic potential. In conclusion, this work presents a new, non-aggressive, easy, inexpensive and reproducible methodology to isolate prospectively cancer stem-like cells for subsequent biological and preclinical studies.
Highlights
Cancer stem cells are responsible for tumor progression, metastasis, therapy resistance and cancer recurrence, doing their identification and isolation of special relevance
Metastatic cancer cells are characterized for suffering an epithelial-to-mesenchymal transition (EMT), a process by which cancer cells lose their attachment to the epithelial niche and acquire a mesenchymal phenotype[10]
Breast cancer stem cell (CSC) are characterized by the phenotype CD44+/CD24low/− 13,14, while the expression of the cell surface proteins CD133, CD44 and/or CD326 is related with colon CSCs properties[15,16,17]
Summary
Cancer stem cells are responsible for tumor progression, metastasis, therapy resistance and cancer recurrence, doing their identification and isolation of special relevance. Our results demonstrate that trypsin-sensitive (TS) breast and colon cancer cells subpopulations show increased ALDH activity, higher ability to exclude Hoechst 33342, enlarged proportion of cells with a cancer stem-like cell phenotype and are enriched in sphere- and colony-forming cells in vitro. Metastatic cancer cells are characterized for suffering an epithelial-to-mesenchymal transition (EMT), a process by which cancer cells lose their attachment to the epithelial niche and acquire a mesenchymal phenotype[10] These cells are transported through the vasculature and are disseminated to anatomically distant organ sites where are able to establish new neoplastic growths[11,12]. The relevance of this cancer cell subpopulation has yield to develop methodologies for their identification and isolation. The isolation of CSCs based on all of these properties requires the fluorescence-activated cell sorting (FACS) method, an expensive and aggressive technique
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