Victor Zhao
Pronouns: He/Him/His
Research Mentor(s): Christopher Oliver
Research Mentor School/College/Department: Michigan Medicine, Internal Medicine Department / Medicine
Program: UROP
Session: Session 2 (10:00am – 10:50am)
Authors: Victor Zhao, Ehsanul Hogue Apu, Huiling Li, Sofia Merajver, C. Ryan Oliver
Abstract
Our understanding of the mechanisms of brain metastasis from breast cancer has been significantly improved by the use of microfluidic organ on a chip (Ooc) blood-brain barrier (BBB) models. These models enable real time long term culture of tumors within a human like brain tumor microenvironment (TME). How the composition of the TME promotes or inhibits tumor growth is poorly understood. Recent work have utilized OoC BBB models to study this problem using a Collagen extracellular matrix. However, the brain micro-environment is primarily composed of hyaluronan/hyaluronic acid (HyA). Because this occupies a large volume of the brain (10-20%) and is composed of important molecules for migration and invasion it may be that selection of the extracellular matrix used in the OoC BBB is important for capturing expected metastatic behavior. Therefore, we have compared the properties of HyA and Collagen in an OoC BBB using MDA-MB-231-BR cancer cells, a brain seeking subclone of MDA-MB-231. We found that migratory patterns of cancer cells differed between the HyA and type I Collagen extracellular matrices. This may be due to significant variations uncovered in the expressions of cancer and tumor-promoting associated biomarkers, including MCP-1, CXCL5, IL-8, DKK1, and SERPIN-E1, found between culture media from MDA-231-BR and normal human astrocyte (NHA) cells grown in collagen and HyA:media mixtures. Additionally, previous studies have shown the stiffness of the brain region to be up to 1 GPa. The storage modulus of undiluted HyA, 1:1 HyA:media, and 1:3 HyA:media were about 60, 5, and 3.5 Pa, respectively. 2% collagen diluted in media was liquid-like and had the lowest stiffness among the samples, much weaker than 0.01 Pa and below the analytical capability of the rheometer used. In conclusion, we have demonstrated that MDA-MB-231-BR cells produced significantly different phenotypes in the OoC BBB which may be due to both biological and biophysical differences between the HyA and Collagen extracellular matrices.
