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"TLR-4 activation of Mesenchymal Stem Cell reverses Breast Cancer Dormancy via Macrophage Polarization"

Nykia D. Walker
Cell Biology, Neuroscience and Physiology Program
B.A. 1999, University of Pennsylvania, Philadelphia, PA
M.S. 2004, Thomas Jefferson University, Philadelphia, PA

Thesis Advisor: Pranela Rameshar, PhD
Department of Medicine
Rutgers New Jersey Medical School

Friday, December 1, 2017
10:00 A.M., MSB C600


Clinical evidence indicates that breast cancer (BC) cells (BCC) can exist in a dormant phase, within the bone marrow (BM) for >10 years. Dormancy occurs when cancer cells undergo cycling quiescence, which can remain undetected until triggered by an activation agent such as stimulation of the pattern recognition receptor. Upon prolonged stimulation, the cells enter cell cycle towards metastasis. Evidence, from our lab and others demonstrate that breast cancer stem cells (B-CSCs), small subset of BCCs, are responsible for BC dormancy and chemotherapy resistance. The mechanisms involved in how B-CSCs promote dormancy and/or subsequent resurgence is under extensive investigation. Previous studies, in our laboratory have reported on gap junctional intercellular communication (GJIC) between B-CSCs and BM stromal cells within the endosteal region. This thesis tested the hypothesis that TLR4-activated mesenchymal stem cells (MSCs) switched the Type 2 macrophage (M2 MÉ∂) into M1 type, resulting in reversed BC dormancy. The results revealed that activated MSCs release exosomes, which facilitate M2 MÉ∂ switch into M1 type. In turn, the M1 MÉ∂ release cytokines to reverse dormancy into metastatic cells. Our findings were correlated with in-vivo mouse studies. The results will be used to develop novel targets to reverse drug-resistant B-CSCs and to prevent dormancy.

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