Reactivation of Breast Cancer Micrometastases by Senescent Bone Marrow Stroma
Abstract
We developed an injury model to bone marrow stroma cultured in vitro from bone marrow samples from mice and human donors. We demonstrated that oxidative injury with H2O2 induces a reproducible time- and dose-dependent secretory senescence profile that consists of export of interleukin 6 (IL-6) by murine and human stroma and IL-8 by murine stroma and activation of TGF beta signaling. Using oxidative injury as a positive control, we demonstrated that estrogen deprivation induces secretory senescence in bone marrow stroma both in female mice and a premenopausal human female volunteer and activation of TGF beta signaling in mice. We defined the parameters for estrogen-induced secretory senescence in mouse and human marrow. Preliminary observations suggest that human marrow is more sensitive to estrogen deprivation-induced secretory senescence resulting in a greater and more sustained response. These data will be expanded to define the relationship between post menopausal status and secretory senescence and the effect on this stromal response on the capacity to support micrometastatic breast cancer cell dormancy.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2010
- Accession Number
- ADA542221
Entities
People
- Robert Wieder
Organizations
- University of Medicine and Dentistry of New Jersey