BME PhD Thesis Defense

David Mertz

Date: Wednesday, November 11, 2020

Time: 1:00PM

Meeting Link: https://bluejeans.com/873836633 

Meeting ID: 873 836 633

Advisor:

Shuichi Takayama, Ph.D.

Committee Members:

Hang Lu, Ph.D. 

Johnna Temenoff, Ph.D. 

Darin Olson, M.D., Ph.D. 

Curtis Henry, Ph.D. 

Title: Inverted Adipose Mammary Microtissues for Early-Stage Tumor Progression Testing

Abstract:  Stromal adipocytes have been increasingly shown to play a role in multiple stages of breast cancer progression. While new culture models are being developed to test hypotheses about interplay between adipose tissue and tumors, none currently exist that recapitulate invasion from the lumen of the mammary duct through a cell-constructed basement membrane into the stromal compartment. Now, we describe a hanging drop culture-based method for producing novel adipocyte-laden mammary microtissues, with a basal side-in architecture, that show potential in their application to early-stage tumor invasion testing. Interestingly, tissues containing adipocytes in a 1:1 ratio with normal epithelium enhance invasion distance by a triple-negative breast cancer cell line three-fold compared to epithelium-only controls. Testing was also conducted using experimental therapies for disrupting CCL5-mediated paracrine chemotaxis and local fibrotic shifts in the microenvironment. The anti-fibrotic drug pirfenidone shows efficacy in the invasion model by slowing invasion at non-toxic concentrations. The use of primary adipocytes in the current model potentially enables its application to a variety of microenvironment models, including for demographic-based comparisons and comorbidities like obesity and diabetes which may require more precise therapeutic testing.