BME PhD Prospectus Defense - Chentian Zhang

2:00 pm on Thursday, November 14, 2013
44 Cummington Mall, Room 203
Committee Members:
Joyce Y. Wong, Ph.D. (Chair)
Mario Cabodi, Ph.D.
Rhoda Alani, M.D.
Catherine Klapperich, Ph.D.
Vickery Trinkaus-Randall, Ph.D.

Title: "Microfluidic System for Cancer Competitive Metastasis"

As cancer metastasis accounts for 90% of all cancer related death, understanding the mechanism of metastasis becomes essential for developing treatments for cancer patients. However, after years of research on cancer metastasis, the mechanism remains largely unsolved. Conventional cancer models in vitro on tissue culture plastic and in vivo using animal models have offered many insights towards understanding this extremely complicated process. However, the poor prediction of clinical outcome based on these models exemplifies the need for a better model to recapitulate the physiologic cancer microenvironment in humans.

The goal of this study is to develop an engineered cancer model that bridges the simplicity of tissue culture plastic models and the complexity of animal models. Harnessing the power of microfabrication and biomimetic materials, the proposed model focuses on studying the last step of cancer metastasis, colonization. We attempt to answer two questions: 1) Why do certain cancers preferentially metastasize to some organs over others? and 2) What is the driving force underlying these preferences? Our engineered metastasis model presents several niches simultaneously to cancer cells, allowing them to interact with each other. By incorporating a biomimetic hydrogel, the cancer cells experience a similar microenvironment as is encountered in vivo. First, we can hope to reproduce the metastatic patterns of cancer cells observed in the clinic in our in vitro model. Then based on the preference of cancer cells we obtained in our model, we can delineate key soluble factors secreted by the preferred niche cells that may account for the cancer’s metastatic preference through a microfluidic gradient generator. The outcome of this study will provide insight into the molecular driving force for cancer metastasis tropism. Moreover, the success of this study will lead to a potential tool to predict the locations of secondary tumors in a personalized medicine fashion for patients who have been diagnosed with primary tumor.