Breast Cancer Osteotropism: Disease Models and the Roles of Mesenchymal Stem Cells.
Abstract: Often the
fields of tissue engineering and cancer research are studied in isolation, inhibiting
cross-talk and collaboration between cancer researchers and tissue engineers. This work
has aimed at bridging these fields in a way that provides insight into the clinical
problems of breast cancer and bone metastasis. The research discussed herein focuses on
how host cells contribute to ... read morethe growth and progression of breast cancer during bone
metastasis. Preliminary studies used the chick CAM, chorioallantoic membrane, to
investigate angiogenesis and bone metastasis (Chapter 2). Then mouse models and
tissue-engineered bone were utilized to study mesenchymal stem cell (MSC) tumor homing
and the effects of MSCs on cancer progression (Chapter 3). Results suggested that
tumor-derived TGF-beta1 (transforming growth factor-beta1) is likely to play a large
role in attracting MSCs to breast tumors in patients. MSC-derived IL-17B (interleukin
17B) was found to stimulate breast cancer cells to metastasize to bone through its
receptor, IL-17BR. Building off these findings, an implant system was developed to
deliver therapeutic or diagnostic MSCs to tumors. TRAIL-MSCs (MSCs that express TRAIL,
an anti-cancer peptide) were investigated for their potential to inhibit tumor cell
growth and current studies are investigating the effectiveness of the TRAIL-hMSC seeded
implants mice (Chapter 4). This work has also investigated a number of different
research areas including fluorescent labeling of stem cells for better tracking of tumor
homing, fibrin microchannel development to study cancer and stem cell migration, spider
silk-based tumor-specific gene delivery, high-throughput screening of cancer drugs in
3-D, stroma-containing systems, and the use of tissue-engineered bone as a target for
breast cancer metastasis (Chapter 5). Lastly, in chapter 6, studies investigating
macrophage-breast cancer cell interactions and findings regarding the relationship
between macrophage polarization and breast cancer cell proliferation are
Thesis (Ph.D.)--Tufts University, 2011.
Submitted to the Dept. of Biomedical Engineering.
Advisor: David Kaplan.
Committee: Jodie Moreau, Jonathan Garlick, and Lauren Black.
Keyword: Biomedical Engineering.read less
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