title: Understanding the impact of 2D and 3D fibroblast cultures on in vitro breast cancer models.
abstract: The utilization of 3D, physiologically relevant in vitro cancer models to investigate complex interactions between tumor and stroma has been increasing. Prior work has generally focused on the cancer cells and, the role of fibroblast culture conditions on tumor-stromal cell interactions is still largely unknown. Here, we focus on the stroma by comparing functional behaviors of human mammary fibroblasts (HMFs) cultured in 2D and 3D and their effects on the invasive progression of breast cancer cells (MCF10DCIS.com). We identified increased levels of several paracrine factors from HMFs cultured in 3D conditions that drive the invasive transition. Using a microscale co-culture model with improved compartmentalization and sensitivity, we demonstrated that HMFs cultured in 3D intensify the promotion of the invasive progression through the HGF/c-Met interaction. This study highlights the importance of the 3D stromal microenvironment in the development of multiple cell type in vitro cancer models.
authors.affiliation: Department of Biomedical Engineering, University of Wisconsin, Madison, Wisconsin, United States of America ; Paul P. Carbone Comprehensive Cancer Center, University of Wisconsin, Madison, Wisconsin, United States of America ; Laboratory of Optical and Computational Instrumentation, University of Wisconsin, Madison, Wisconsin, United States of America.
authors.forename: Kyung Eun
authors.initials: KE
authors.lastname: Sung
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Su
authors.forename: Erwin
authors.initials: E
authors.lastname: Berthier
authors.forename: Carolyn
authors.initials: C
authors.lastname: Pehlke
authors.forename: Andreas
authors.initials: A
authors.lastname: Friedl
authors.forename: David J
authors.initials: DJ
authors.lastname: Beebe
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis; D006801:Humans; D042361:Mammary Glands, Human / Q000166:cytology / Q000378:metabolism; D046210:Microfluidic Analytical Techniques / Q000379:methods; D009361:Neoplasm Invasiveness; D010641:Phenotype; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology
chemical_list: D017228:Hepatocyte Growth Factor