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In Vitro Models for Studying Invasive Transitions of Ductal Carcinoma In Situ

  • Ethan J. Brock
  • Kyungmin Ji
  • Seema Shah
  • Raymond R. Mattingly
  • Bonnie F. Sloane
Article

Abstract

About one fourth of all newly identified cases of breast carcinoma are diagnoses of breast ductal carcinoma in situ (DCIS). Since we cannot yet distinguish DCIS cases that would remain indolent from those that may progress to life-threatening invasive ductal carcinoma (IDC), almost all women undergo aggressive treatment. In order to allow for more rational individualized treatment, we and others are developing in vitro models to identify and validate druggable pathways that mediate the transition of DCIS to IDC. These models range from conventional two-dimensional (2D) monolayer cultures on plastic to 3D cultures in natural or synthetic matrices. Some models consist solely of DCIS cells, either cell lines or primary cells. Others are co-cultures that include additional cell types present in the normal or cancerous human breast. The 3D co-culture models more accurately mimic structural and functional changes in breast architecture that accompany the transition of DCIS to IDC. Mechanistic studies of the dynamic and temporal changes associated with this transition are facilitated by adapting the in vitro models to engineered microfluidic platforms. Ultimately, the goal is to create in vitro models that can serve as a reproducible preclinical screen for testing therapeutic strategies that will reduce progression of DCIS to IDC. This review will discuss the in vitro models that are currently available, as well as the progress that has been made using them to understand DCIS pathobiology.

Keywords

2D cultures 3D cultures Co-cultures Tumor microenvironment Natural matrices Synthetic matrices Engineered microfluidic platforms Preclinical screens 

Abbreviations

2D

Two-dimensional

3D

Three-dimensional

DCIS

Ductal carcinoma in situ

IDC

Invasive ductal carcinoma

ER

Estrogen receptor

PR

Progesterone receptor

HER2

Human epidermal growth factor receptor 2

SIM2s

Singleminded-2s

TNBCs

Triple-negative breast cancers

EGF

Epidermal growth factor

EGFR

Epidermal growth factor receptor

HGF

Hepatocyte growth factor

MET

Hepatocyte growth factor receptor

PPARγ

Peroxisome proliferator-activated receptor gamma

rBM

Reconstituted basement membrane

MMP

Matrix metalloproteinase

ECM

Extracellular matrix

LAMP2

Lysosome-associated membrane protein-2

CCL20

C-C motif chemokine ligand 20

CAF

Carcinoma-associated fibroblast

MEPs

Myoepithelial cells

DQ

Dye quenched

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018
corrected publication August/2018

Authors and Affiliations

  1. 1.Program in Cancer BiologyWayne State University School of MedicineDetroitUSA
  2. 2.Department of PharmacologyWayne State University School of MedicineDetroitUSA
  3. 3.Department of PharmacologyWayne State UniversityDetroitUSA

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