Project Two: Cellular Dormancy
Multiple mechanics used by MSCs to induce stromal cell reprogramming to facilitate breast cancer dormancy: A) MSC derived exosomal cargo, like miRs can reprogram breast cancer cells (BCCs). B) MSC secretion of SDF-1 to form gap junction with stromal cells. C) MSC reverse dormancy by altering stromal cell function. D) MSC induced T cell conversion to Tregs by TGF-B secretion.
MSC-induced cellular dormancy is mediated through various mechanisms, including inhibition of cell proliferation, induction of cell cycle arrest, modulation of immune surveillance, and alteration of the tumor microenvironment. Our lab focuses on how MSC derived exosomes are used to reprogram other stromal cells to support cellular dormancy in the bone marrow endosteum. The bone marrow is the location of hematopoietic stem cells, but also becomes the area where disseminating breast cancer cells migrate and undergo cellular dormancy. Understanding the mechanisms involved is crucial for developing strategies to prevent relapse and to improve treatment outcomes for patients with metastatic breast cancer.
Relevant Publications:
Walker ND, Elias M, Guiro K, Bhatia R, Greco SJ, Bryan M, Ponzio, NM, Leibovich, SJ and Rameshwar, P. Exosomes from differentially activated macrophage influence dormancy or resurgence of breast cancer cell within the bone marrow stroma. Cell Death Dis. 2019; 59 (10).
Patel JS, Hu M, Sinha G, Walker ND, Sherman LS, Gallagher A, Rameshwar P., Non-coding RNA as mediators in microenvironment–breast cancer cell communication. Cancer Lett 2016 Sep 28;380(1):289-95.
Walker ND, Patel J, Munoz JL, Hu M, Guiro K, Sinha G, Rameshwar P. The bone marrow niche in support of breast cancer dormancy. Cancer Lett 2015; S0304-3835(15)00664-3.
Walker ND, Nahas GR, Munoz J, Lucas J, Pobiarzyn P, Rameshwar, P. Mesenchymal Stromal Cells as Tumor Stromal Modulators. 1st Edition. 2016, p. 425-447.
Munoz, JL*, Walker ND*, Greco, SJ and Rameshwar, P. Cycling quiescence in temozolomide resistant glioblastoma cells is partly explained by microRNA-93 and 193 mediated decreased of cyclin D. Front. Pharmacol., section Cancer Molecular Targets and Therapeutics. 22 February 2019.
Munoz, JL*, Walker ND*, Greco, SJ., and Rameshwar, P., Temozolomide competes for P-glycoprotein to impart chemoresistance in glioblastoma cells. Cancer Lett 2015;367(1):69-75.
Nahas GR., Walker ND., Rameshwar P. A perspective of immune therapy for breast cancer: Lessons learnt and forward directions. Breast Cancer: Basic Clin Res. 2015; 9(Suppl2):35-43.
The team members involved in Project 2 are called “the sleepy slayers” because they are on a mission to identify ways to wake up dormant breast cancer stem cells as a therapeutic strategy to treat metastatic breast cancer.
Meet the Sleepy Slayers
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Nykia Walker
The Original Sleepy Slayer
Dr. Walker investigates how bone marrow stroma, such as MSCs, adipocytes and macrophage maintain breast cancer cellular dormancy in the bone marrow.
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Irina Sbornova
Ultimate Sleepy Slayer Alumni
Irina developed a quantitation tool to study adipose browning and cancer associated adipocytes as a potential predictor of breast cancer metastasis.
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Mohammad Mikail Iftekhar Bala
Sleepy Samurai Bioinformatician
Mohammad is a master student in the lab who performed bioinformatics analysis that identified key miRNAs involved in macrophage polarization and cellular dormancy.
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Join our team
We are recruiting new team members to help us discover mechanisms used by breast cancer stem cells to maintain cellular dormancy in the bone marrow.
Funding
