Altering the Microenvironment to Promote Dormancy of Metastatic Breast Cancer Cell in a 3D Bone Culture System
Technical Report,01 Apr 2012,30 Sep 2015
Pennsylvania State University University Park United States
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Hypothesis extracellular matrix ECM and bone microenvironment cytokines are critical for metastatic breast cancer cells to grow or remain dormant. This hypothesis was tested using a 3D bioreactor of ECM, derived from osteoblastsOB. Aim 1 determine how modification of the composition and structure of the ECM affects proliferation and dormancy. 1a.deprive OB of estrogen 1b. stress the ECM 1c. degrade the ECM with osteoclasts. Aim 2. determine how bone-remodeling and inflammatory cytokines affect proliferation and dormancy. 2a. addblock bone remodeling cytokines, 2b. addblock OB inflammatory stress response cytokines. The remodeling but not inflammatory cytokines permit dormant human cells to proliferate in the bioreactor in co-culture with OB. Proliferation depended on prostaglandin, PGE2 production. Chronicoxidative stress of the ECM with H2O2 did not affect cancer cell growth. However estrogen deprivation or blocking the estrogen receptor permitted the dormant cells to proliferate. Human breast cancer cells grew better on decellularized matrix or on fixed osteoblasts than on intact matrix indicating that OB produce factors antagonistic to cancer cells.