| First Author | Gilbert LA | Year | 2010 |
| Journal | Cell | Volume | 143 |
| Issue | 3 | Pages | 355-66 |
| PubMed ID | 21029859 | Mgi Jnum | J:208977 |
| Mgi Id | MGI:5565452 | Doi | 10.1016/j.cell.2010.09.043 |
| Citation | Gilbert LA, et al. (2010) DNA damage-mediated induction of a chemoresistant niche. Cell 143(3):355-66 |
| abstractText | 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. |
