Subtype-specific characterization of breast cancer invasionusing a microfluidic tumor platform.

Hye-Ran Moon,Victoria Noe-Kim,Yi Yang,Natalia Ospina-Muñoz,Bumsoo Han,Stephen F Konieczny,Bennett D Elzey,Jonghoon Choi

doi:10.1371/journal.pone.0234012

Hye-Ran Moon, Victoria Noe-Kim + Show 6 more

Open Access

https://doi.org/10.1371/journal.pone.0234012

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Abstract

Understanding progression of breast cancers to invasive ductal carcinoma (IDC) can significantly improve breast cancer treatments. However, it is still difficult to identify genetic signatures and the role of tumor microenvironment to distinguish pathological stages of pre-invasive lesion and IDC. Presence of multiple subtypes of breast cancers makes the assessment more challenging. In this study, an in-vitro microfluidic assay was developed to quantitatively assess the subtype-specific invasion potential of breast cancers. The developed assay is a microfluidic platform in which a ductal structure of epithelial cancer cells is surrounded with a three-dimensional (3D) collagen matrix. In the developed platform, two triple negative cancer subtypes (MDA-MB-231 and SUM-159PT) invaded into the surrounding matrix but the luminal A subtype, MCF-7, did not. Among invasive subtypes, SUM-159PT cells showed significantly higher invasion and degradation of the surrounding matrix than MDA-MB-231. Interestingly, the cells cultured on the platform expressed higher levels of CD24 than in their conventional 2D cultures. This microfluidic platform may be a useful tool to characterize and predict invasive potential of breast cancer subtypes or patient-derived cells.

Highlights

Breast cancers often start from ductal carcinoma in situ (DCIS), in which abnormal epithelial cells are present in the mammary ducts of breast tissues. [1, 2] This pre-cancerous lesion progresses to invasive ductal carcinoma (IDC), which will need major treatments including chemotherapy, radiation, and surgical therapies. [3,4,5] Understanding and characterization of the transition of DCIS into IDC can significantly improve the treatment and management of breast cancers
The ducts consist of a layer of epithelial cells in the lining covered by myoepithelial cells and basement membrane (BM) [36]
The present model is capable of recapitulating cancer invasion as key pathophysiological processes as well as predicting the invasive potential of subtypes of breast cancer cells

Summary

Introduction

Breast cancers often start from ductal carcinoma in situ (DCIS), in which abnormal epithelial cells are present in the mammary ducts of breast tissues. [1, 2] This pre-cancerous lesion progresses to invasive ductal carcinoma (IDC), which will need major treatments including chemotherapy, radiation, and surgical therapies. [3,4,5] Understanding and characterization of the transition of DCIS into IDC can significantly improve the treatment and management of breast cancers. Breast cancers often start from ductal carcinoma in situ (DCIS), in which abnormal epithelial cells are present in the mammary ducts of breast tissues. [1, 2] This pre-cancerous lesion progresses to invasive ductal carcinoma (IDC), which will need major treatments including chemotherapy, radiation, and surgical therapies. [3,4,5] Understanding and characterization of the transition of DCIS into IDC can significantly improve the treatment and management of breast cancers.

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