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The Role of CD90 in Breast Cancer Tumor Progression

thesis
posted on 29.07.2020 by Monica Chanda

Breast cancer is the most common cancer among women, with effective treatments if the disease stays local. However, if the tumor metastasizes, patient outcomes are significantly reduced. Mesenchymal stem cells (MSC) have been shown to enhance metastasis by facilitating invasion and tumor outgrowth. MCF10A Ca1h cells, a mesenchymal-like cell line, have been shown to promote metastasis in a murine model and enhance the survival and proliferation of their epithelial counterpart (Ca1a) in coculture. We have established the presence of the classic MSC markers, CD90, CD105, and CD73, on the Ca1h cells and observe a decrease in the CD90+ population in the Ca1a and fibronectin knockdown Ca1h cells. To examine the effects of this decreased expression, a CD90 knockdown of Ca1h cells was created using lenti-viral transduction. A decrease in fibronectin levels was seen in the CD90 knockdowns, along with a change in morphological characteristics of the cells. To investigate the influence of a 3D microenvironment on cell phenotype, they were also cultured on fibronectin coated scaffolds and evaluated for CD44/CD24 expression. Lastly, the knockdowns were cocultured with the Ca1a cells in a 3D hydrogel to assess the impact of coculture on survival and proliferation. We found that the CD90 knockdowns take on epithelial-like characteristics and decrease survival of Ca1a cells in coculture. These findings suggest that CD90 is necessary to maintain a mesenchymal phenotype and could be used as a target for therapies to prevent metastasis.

Funding

R0CA19829

History

Degree Type

Master of Science in Biomedical Engineering

Department

Biomedical Engineering

Campus location

West Lafayette

Advisor/Supervisor/Committee Chair

Dr. Luis Solorio

Additional Committee Member 2

Dr. Michael Wendt

Additional Committee Member 3

Dr. Sherry Harbin

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