Stem-like and highly invasive prostate cancer cells expressing CD44v8-10 marker originate from CD44-negative cells
| Autor: | Paola Grazioli, Antonella Stoppacciaro, Chiara Di Stefano, Margherita Pesce, Antonella D'Amore, Anna Riccioli, Michele Regno, Fabrizio Padula, Rosaria Anna Fontanella, Rita Canipari, Antonio Filippini, Elio Ziparo, Paola De Cesaris, Micol Elena Fiori, Donatella Starace, Antonio Francesco Campese |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Population Cell Biology 03 medical and health sciences Prostate cancer Prostate stem cells Alternative splicing CD44 Invasiveness alternative splicing invasiveness prostate stem cells medicine education Clonogenic assay education.field_of_study Cancer medicine.disease 030104 developmental biology medicine.anatomical_structure Oncology Cell culture Cancer research biology.protein Stem cell Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | In human prostate cancer (PCa), the neuroendocrine cells, expressing the prostate cancer stem cell (CSC) marker CD44, may be resistant to androgen ablation and promote tumor recurrence. During the study of heterogeneity of the highly aggressive neuroendocrine PCa cell lines PC3 and DU-145, we isolated and expanded in vitro a minor subpopulation of very small cells lacking CD44 (CD44neg). Unexpectedly, these sorted CD44neg cells rapidly and spontaneously converted to a stable CD44high phenotype specifically expressing the CD44v8-10 isoform which the sorted CD44high subpopulation failed to express. Surprisingly and potentially interesting, in these cells expression of CD44v8-10 was found to be induced in stem cell medium. CD44 variant isoforms are known to be more expressed in CSC and metastatic cells than CD44 standard isoform. In agreement, functional analysis of the two sorted and cultured subpopulations has shown that the CD44v8-10pos PC3 cells, resulting from the conversion of the CD44neg subpopulation, were more invasive in vitro and had a higher clonogenic potential than the sorted CD44high cells, in that they produced mainly holoclones, known to be enriched in stem-like cells. Of interest, the CD44v8-10 is more expressed in human PCa biopsies than in normal gland. The discovery of CD44v8-10pos cells with stem-like and invasive features, derived from a minoritarian CD44neg cell population in PCa, alerts on the high plasticity of stem-like markers and urges for prudency on the approaches to targeting the putative CSC. |
| Databáze: | OpenAIRE |
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