BME PhD Dissertation Defense - Yoseph Dance

   
Summary

BME PhD Dissertation Defense - Yoseph Dance

Description

Title: "Engineering three-dimensional breast tumor-on-a-chips to investigate the roles of adipose tissue and obesity in the early stages of breast cancer metastasis"

Advisory Committee: Béla Suki, PhD – BU BME (Chair) Joe Tien, PhD – BU BME (Advisor) Ji-Xin Cheng, PhD – BU BME Tova Meshulam, PhD – BUSM Biochemistry Matthew Layne, PhD – BUSM Biochemistry

Abstract: The mechanisms by which malignant human breast cancer cells invade the interstitial space, intravasate into vasculature, and metastasize at secondary sites in the body are recently beginning to be appreciated. On the other hand, little is known about how the stroma surrounding a breast tumor modifies the initial steps of the metastatic process, in part because long-term imaging of these steps in vivo is extremely challenging. Microfluidic in vitro “tumor on-a-chip” devices can shed light on these issues since these platforms can be readily imaged over time and maintain precise control over key features of the breast tumor microenvironment, including extracellular matrix (ECM) composition, interstitial fluid pressure (IFP), and a plethora of stromal and vascular structures. In this dissertation, I present a variety of 3D breast tumor-on-a-chip platforms that contain at least one of these key features, with a particular emphasis on adipose tissue, a primary constituent of the human breast. My work provides insight into how adipose tissue and other select features of the stroma surrounding the human breast contribute to the interstitial invasion and vascular escape of human breast cancer cells.

Adipocytes and adipose-derived stem cells (ASCs), hereby referred to collectively as adipose cells, hasten breast cancer cell invasion and escape. These effects are mediated by adipose cell-secreted soluble factors that act directly on tumor cells. ASCs are the more potent source of these invasion- and escape-enhancing factors. Surprisingly, a variety of obesity-associated features do not modify adipose cell-promoted invasion or escape. In particular, neither the donor obesity status of ASCs or adipocytes, nor the hypertrophy of adipocytes, alters the rate of adipose stroma-promoted escape.

These 3D breast tumor-on-a-chip platforms have shed light on the links between adipose stroma, obesity, and the early steps of breast cancer metastasis, and serve as a baseline for future in vitro models of human breast cancer progression.

Starts

11:00am on Wednesday, December 14th 2022

Location

8 St. Mary’s St, room 901 (PHO)

Topics

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