Accession Number:

ADA604844

Title:

Altering the Microenvironment to Promote Dormancy of Metastatic Breast Cancer Cell in a 3D Bone Culture System

Descriptive Note:

Annual rept. 1 Apr 2013-31 Mar 2014

Corporate Author:

PENNSYLVANIA STATE UNIV STATE COLLEGE

Personal Author(s):

Report Date:

2014-04-01

Pagination or Media Count:

16.0

Abstract:

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. addblock bone remodeling cytokines, 2b. addblock OB inflammatory stress response cytokines. Thus far the remodeling cytokines permit dormant human cells to proliferate in the bioreactor in co-culture with OB. The effect appears to depend on prostaglandin 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 factors antagonistic to cancer cells.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE