Abstract

Breast cancer (BC) is the most frequently diagnosed malignancy among women globally. Although mouse models have been critical in advancing the knowledge of BC tumorigenesis and progression, human breast models comprising the breast tissue microenvironment are needed to help elucidate the underlying mechanisms of BC risk factors. As such, it is essential to identify an ex vivo human breast tissue mimetic model that can accurately pinpoint the effects of these factors in BC development. While two-dimensional models have been invaluable, they are not suitable for studying patient-specific tumor biology and drug response. Recent developments in three-dimensional (3D) models have led to the prominence of organized structures grown in a 3D environment called “organoids.” Breast organoids can accurately recapitulate the in vivo breast microenvironment and have been used to examine factors that affect signaling transduction, gene expression, and tissue remodeling. In this review, the applications, components, and protocols for development of breast organoids are discussed. We summarize studies that describe the utility of breast organoids, including in the study of normal mammary gland development and tumorigenesis. Finally, we provide an overview of protocols for development of breast organoids, and the advantages and disadvantages of different techniques in studies are described. The included studies have shown that breast organoids will continue to serve as a crucial platform for understanding of progression of BC tumors and the testing of novel therapeutics.

Highlights

  • Breast cancer (BC) is the most frequently diagnosed malignancy among women (Momenimovahed and Salehiniya 2019)

  • Much effort has been focused on understanding breast cancer tumorigenesis

  • Mouse models have been critical in advancing the knowledge of breast cancer tumorigenesis and progression, human breast models comprising the breast tissue microenvironment are needed to help elucidate the underlying mechanisms of BC risk factors

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Summary

INTRODUCTION

Breast cancer (BC) is the most frequently diagnosed malignancy among women (Momenimovahed and Salehiniya 2019). 3D culture is useful in the examination of types of progenitor cells in the breast, as demonstrated by studies utilizing normal human mammary epithelial organoids (Villadsen et al, 2007; Fridriksdottir et al, 2017). Matrix stiffness is an important feature as it alters epithelial morphogenesis by clustering integrins and regulates cell fate by modulating growth factor signaling and Rho GTPase function (Paszek et al, 2005). Current matrices include both natural and synthetic scaffolds. Much less commonly utilized in breast organoid culture, synthetic scaffolds include polymers that retain the mechanical properties of the tumors, such as polyethylene glycol, polyvinyl alcohol, polycaprolactone, and polylactide-co-glycolide, their stiffness may not be as similar to in vivo tissue as that of naturally derived scaffolds (Rimann and Graf-Hausner 2012)

Discussion of Breast Organoid Protocols
Significance of study
CONCLUSION
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