Your browser doesn't support javascript.

Biblioteca Virtual em Saúde

Brasil

Home > Pesquisa > ()
Imprimir Exportar

Formato de exportação:

Exportar

Email
Adicionar mais destinatários
| |

DNA damage-mediated induction of a chemoresistant niche.

Gilbert, Luke A; Hemann, Michael T.
Cell; 143(3): 355-66, 2010 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-21029859
While numerous cell-intrinsic processes are known to play decisive roles in chemotherapeutic response, relatively little is known about the impact of the tumor microenvironment on therapeutic outcome. Here, we use a well-established mouse model of Burkitt's lymphoma to show that paracrine factors in the tumor microenvironment modulate lymphoma cell survival following the administration of genotoxic chemotherapy. Specifically, IL-6 and Timp-1 are released in the thymus in response to DNA damage, creating a "chemo-resistant niche" that promotes the survival of a minimal residual tumor burden and serves as a reservoir for eventual tumor relapse. Notably, IL-6 is released acutely from thymic endothelial cells in a p38-dependent manner following genotoxic stress, and this acute secretory response precedes the gradual induction of senescence in tumor-associated stromal cells. Thus, conventional chemotherapies can induce tumor regression while simultaneously eliciting stress responses that protect subsets of tumor cells in select anatomical locations from drug action.
Selo DaSilva