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|a Gilbert, Luke Andrew
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|a Massachusetts Institute of Technology. Department of Biology
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|a Koch Institute for Integrative Cancer Research at MIT
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|a Hemann, Michael
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|a Gilbert, Luke Andrew
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|a Hemann, Michael
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|a DNA Damage-Mediated Induction of a Chemoresistant Niche
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|b Elsevier B.V.,
|c 2015-03-19T14:57:12Z.
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|z Get fulltext
|u http://hdl.handle.net/1721.1/96076
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|a 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.
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|a National Institutes of Health (U.S.) (NIH RO1 CA128803)
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|a David H. Koch Institute for Integrative Cancer Research at MIT (Ludwig Center for Molecular Oncology))
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|a Massachusetts Institute of Technology. Department of Biology (Rita Allen Fellow)
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|a en_US
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|a Article
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|t Cell
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