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首页> 美国政府科技报告 >Altering the Microenvironment to Promote Dormancy of Metastatic Breast Cancer Cell in a 3D Bone Culture System.
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Altering the Microenvironment to Promote Dormancy of Metastatic Breast Cancer Cell in a 3D Bone Culture System.

机译：改变微环境促进转移性乳腺癌细胞在3D骨培养系统中的休眠。

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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 is being tested using a 3D bioreactor of ECM, derived from osteoblasts (OB). 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. add/block bone remodeling cytokines, 2b. add/block 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. Chronic oxidative stress of the ECM with H2O2 did not affect cancer cell growth. Howver estrogen deprivation or blocking the estrogen receptor permitted the dormant cells to proliferate. Human breast cancer cells grew better on decellurized matrix or on fixed osteoblasts than on intact matrix indicating that OB produce factor(s) antagonistic to cancer cells.

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