Pathomimetic avatars reveal divergent roles of microenvironment in invasive transition of ductal carcinoma in situ

Breast Cancer Research : BCR
Mansoureh SameniBonnie F Sloane

Abstract

The breast tumor microenvironment regulates progression of ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC). However, it is unclear how interactions between breast epithelial and stromal cells can drive this progression and whether there are reliable microenvironmental biomarkers to predict transition of DCIS to IDC. We used xenograft mouse models and a 3D pathomimetic model termed mammary architecture and microenvironment engineering (MAME) to study the interplay between human breast myoepithelial cells (MEPs) and cancer-associated fibroblasts (CAFs) on DCIS progression. Our results show that MEPs suppress tumor formation by DCIS cells in vivo even in the presence of CAFs. In the in vitro MAME model, MEPs reduce the size of 3D DCIS structures and their degradation of extracellular matrix. We further show that the tumor-suppressive effects of MEPs on DCIS are linked to inhibition of urokinase plasminogen activator (uPA)/urokinase plasminogen activator receptor (uPAR)-mediated proteolysis by plasminogen activator inhibitor 1 (PAI-1) and that they can lessen the tumor-promoting effects of CAFs by attenuating interleukin 6 (IL-6) signaling pathways. Our studies using MAME are, to our knowledge, the first to demon...Continue Reading

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Citations

Nov 1, 2017·The Journal of Pathology·Hendrika M DuivenvoordenBelinda S Parker
Jun 26, 2020·Advanced Healthcare Materials·Eric ParigorisShuichi Takayama
Jul 30, 2018·Journal of Mammary Gland Biology and Neoplasia·Ethan J BrockBonnie F Sloane
Sep 9, 2018·Journal of Mammary Gland Biology and Neoplasia·Vidya C Sinha, Helen Piwnica-Worms
Sep 1, 2018·Journal of Mammary Gland Biology and Neoplasia·Andrew C NelsonKathryn L Schwertfeger
Aug 24, 2018·Journal of Experimental & Clinical Cancer Research : CR·Hoe Suk KimWoo Kyung Moon
Jul 3, 2021·Cancers·Patricia Fernández-NogueiraPaloma Bragado

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Methods Mentioned

BETA
xenograft
protein assay
xenografts

Software Mentioned

MAME
Mascot
Prism
Volocity
GraphPad

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