Cancer stem cells – new and potentially important targets for the therapy of oral squamous cell carcinoma

Abstract

There is increasing evidence that the growth and spread of cancers is driven by a small subpopulation of cancer stem cells (CSCs) - the only cells that are capable of long-term self-renewal and generation of the phenotypically diverse tumour cell population. Current failure of cancer therapies may be due to their lesser effect on potentially quiescent CSCs which remain vital and retain their full capacity to repopulate the tumour. Treatment strategies for the elimination of cancer therefore need to consider the consequences of the presence of CSCs. However, the development of new CSC-targeted strategies is currently hindered by the lack of reliable markers for the identification of CSCs and the poor understanding of their behaviour and fate determinants. Recent studies of cell lines derived from oral squamous cell carcinoma (OSCC) indicate the presence of subpopulations of cells with phenotypic and behavioural characteristics corresponding to both normal epithelial stem cells and to cells capable of initiating tumours in vivo. The present review discusses the relevance to OSCC of current CSC concepts, the state of various methods for CSC identification, characterization and isolation (clonal functional assay, cell sorting based on surface markers or uptake of Hoechst dye), and possible new approaches to therapy.

Cancer stem cells as targets for cancer therapy: selected cancers as examples

“…The treatment strategies of OSCC are based on the idea that oral cancer is generated by a population of cells of equal proliferative and aggressive potential [37]. More recent reports suggest that the CSC hypothesis may likely also apply to OSCC [37,68].…”

“…More recent reports suggest that the CSC hypothesis may likely also apply to OSCC [37,68]. There are various possible scenarios by which OSCC could originate from stem cells: (a) it develops directly from malignant stem cells or (b) a tumorigenic potential is promoted in the supra-basal compartment when differentiating cells deviate from their predetermined differentiation route and transform into malignant intra-epithelial cells.…”

Análise da expressão de receptores hormonais (androgênio, estrogênio alfa e beta) e da aromatase em carcinomas epidermóides de boca (CE)

“…Ocorre de forma geral, em adultos entre quinta e sexta décadas de vida, com predileção pelo gênero masculino (SIlverman, 2001;Barnes et al, 2005;Bagan, 2009;Marocchio et al, 2010 (Costea et al, 2006).…”

“…3-células diferenciadas (Costea et al, 2006) A camada basal é tida como a localização anatômica de células-tronco/específicas progenitoras do tecido epitelial (Tudor et al, 2004). Têm sido descritas como maior alvo de mutações que podem levar ao câncer.…”

“…Têm sido descritas como maior alvo de mutações que podem levar ao câncer. Essas mutações são consideradas de alto risco tanto para a transformação maligna, quanto para a progressão tumoral (Costea et al, 2006). A longevidade das células-tronco faz com que sejam mais susceptíveis acumulem danos genéticos durante a renovação celular e se tornem alvos para a transformação carcinogênica .…”