Three-Dimensional Models as a New Frontier for Studying the Role of Proteoglycans in the Normal and Malignant Breast Microenvironment

Julien Clegg; Maria K Koch; Erik W Thompson; Larisa M Haupt; Priyakshi Kalita-de Croft; Laura J Bray

doi:10.3389/fcell.2020.569454

Three-Dimensional Models as a New Frontier for Studying the Role of Proteoglycans in the Normal and Malignant Breast Microenvironment

Front Cell Dev Biol. 2020 Oct 9:8:569454. doi: 10.3389/fcell.2020.569454. eCollection 2020.

Authors

Julien Clegg¹, Maria K Koch¹, Erik W Thompson^{1

2

3}, Larisa M Haupt^{1

2

4}, Priyakshi Kalita-de Croft⁵, Laura J Bray^{1

3

6}

Affiliations

¹ Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, QLD, Australia.
² School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD, Australia.
³ Translational Research Institute, Woolloongabba, QLD, Australia.
⁴ Centre for Genomics and Personalized Health, Genomics Research Centre, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, QLD, Australia.
⁵ UQ Centre for Clinical Research, Faculty of Medicine, University of Queensland, Herston, QLD, Australia.
⁶ Faculty of Science and Engineering, School of Mechanical, Medical and Process Engineering, Queensland University of Technology, Brisbane, QLD, Australia.

Abstract

The extracellular matrix (ECM) provides cues to direct mammogenesis, tumourigenesis and metastatic processes. Over the past several decades, two-dimensional (2D) culture models have been invaluable in furthering our understanding of the tumor microenvironment (TME), however, they still do not accurately emulate the associated biological complexities. In contrast, three-dimensional (3D) culture models provide a more physiologically relevant platform to study relevant physicochemical signals, stromal-epithelial cell interactions, vascular and immune components, and cell-ECM interactions in the human breast microenvironment. A common thread that may weave these multiple interactions are the proteoglycans (PGs), a prominent family of molecules in breast tissue. This review will discuss how these PGs contribute to the breast cancer TME and provide a summary of the traditional and emerging technologies that have been utilized to better understand the role of PGs during malignant transformation. Furthermore, this review will emphasize the differences that PGs exhibit between normal tissues and tumor ECM, providing a rationale for the investigation of underexplored roles of PGs in breast cancer progression using state-of-the-art 3D culture models.

Keywords: 3D models; breast cancer; extracellular matrix (ECM); proteoglycans (PGs); tumor microenvironment (TME).

Publication types

Review