Autor(es):
Rodrigues, Carlos F. D. ; Serrano, Eurico ; Patrício, Maria I. ; Val, Mariana ; Albuquerque, Patrícia ; Fonseca, João ; Gomes, Célia M. F. ; Abrunhosa, Antero ; Paiva, Artur ; Carvalho, Lina ; Botelho, Maria F. ; Almeida, Luís ; Carreira, Isabel M. ; Alpoim, Maria Carmen
Data: 2018
Identificador Persistente: https://hdl.handle.net/10316/108042
Origem: Estudo Geral - Universidade de Coimbra
Assunto(s): Activins; Animals; Carcinogenesis; Cell Differentiation; Cell Line, Tumor; Coculture Techniques; Granulocyte Colony-Stimulating Factor; Humans; Interleukin-6; Mice, Inbred BALB C; Mice, SCID; Neoplasms, Experimental; Neoplastic Stem Cells; Stromal Cells
Descrição
Cancer stem cells (CSCs) are a small population of resistant cells inhabiting the tumors. Although comprising only nearly 3% of the tumor mass, these cells were demonstrated to orchestrate tumorigenesis and differentiation, underlie tumors' heterogeneity and mediate therapy resistance and tumor relapse. Here we show that CSCs may be formed by dedifferentiation of terminally differentiated tumor cells under stress conditions. Using a elegant co-culture cellular system, we were able to prove that nutrients and oxygen deprivation activated non-malignant stromal fibroblasts, which in turn established with tumor cells a paracrine loop mediated by Interleukine-6 (IL-6), Activin-A and Granulocyte colony-stimulating factor (G-CSF), that drove subsequent tumor formation and cellular dedifferentiation. However, by scavenging these cytokines from the media and/or blocking exosomes' mediated communication it was possible to abrogate dedifferentiation thus turning these mechanisms into potential therapeutic targets against cancer progression.
