Grantee Research Project Results

Cancer MAPs: A 3D Organotypic Microfluidic Culture System to Identify Chemicals that Impact Progression and Development of Breast Cancer

EPA Grant Number: R835737C003
Subproject: this is subproject number 003 , established and managed by the Center Director under grant R835737
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: Human Models for Analysis of Pathways (H MAPs) Center
Center Director: Murphy, William L
Title: Cancer MAPs: A 3D Organotypic Microfluidic Culture System to Identify Chemicals that Impact Progression and Development of Breast Cancer
Investigators: Beebe, David , Murphy, William L
Institution: University of Wisconsin - Madison
EPA Project Officer: Aja, Hayley
Project Period: December 1, 2014 through November 30, 2018 (Extended to November 30, 2019)
RFA: Organotypic Culture Models for Predictive Toxicology Center (2013) RFA Text | Recipients Lists
Research Category: Chemical Safety for Sustainability

Objective:

The effects of chemicals present in the environment on human health are poorly understood. Exposure to toxicants has been identified as a major preventable risk factor for breast cancer, the leading cause of cancer-related death among women worldwide. The primary objective of this project is to develop, validate and use a reliable 3D high-throughput screening platform to explore the influence of chemicals on the different stages of breast cancer development. We hypothesize that certain chemicals will affect hormone-responsive mammary epithelial cells differently at each stage of breast cancer. In Aim 1 we will optimize and automate our synchronous microfluidic 3D in vitro breast cancer model to be used for chemical library screening. In Aim 2 we will develop an adverse outcome pathway (AOP) based model of estrogen-receptor (ER) mediated invasive ductal carcinoma (IDC) by utilizing quantitative physiological and molecular endpoints to identify key steps between the initiating event (estrogen receptor ligand binding) and the adverse outcome (IDC) in our microfluidic platform. Then, in Aim 3, we will conduct low- and medium-throughput screens using chemicals from the ToxCast library in our organotypic system to identify chemicals that promote ER-mediated and non ER-mediated IDC. Completion of the project as described will produce an organotypic culture model (OCM) of breast cancer compatible with higher throughput screening (HTS) and high-content (HCS) screening approaches to discern toxic effects of chemical substances on breast cancer development and progression.

Publications and Presentations:

Publications have been submitted on this subproject: View all 6 publications for this subproject | View all 215 publications for this center

Journal Articles:

Journal Articles have been submitted on this subproject: View all 6 journal articles for this subproject | View all 81 journal articles for this center

Supplemental Keywords:

ductal carcinoma in situ (DCIS), estrogen disrupting chemicals (EDC), extracellular matrix (ECM), lumen, mammary duct, microenvironment, microfluidics, stroma, xenoestrogens

Progress and Final Reports:

Main Center Abstract and Reports:

R835737 Human Models for Analysis of Pathways (H MAPs) Center

Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R835737C001 Liver MAPs
R835737C002 Brain MAPs
R835737C003 Cancer MAPs: A 3D Organotypic Microfluidic Culture System to Identify Chemicals that Impact Progression and Development of Breast Cancer
R835737C004 Vascular MAPs: Vascular and Neurovascular Tissue Models
R835737C005 Pathway Analysis Core

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The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.