Page 249 - Read Online

Mooney et al. J Cancer Metastasis Treat 2019;5:19 Journal of Cancer
DOI: 10.20517/2394-4722.2018.93 Metastasis and Treatment

Original Article Open Access

Understanding convergent signaling regulation
in metastatic breast cancer cells using a

bioengineered stem cell microenvironment

Bridget Mooney, Yangzi Isabel Tian, Erin Rousseau, Yubing Xie

Colleges of Nanoscale Science and Engineering, SUNY Polytechnic Institute, Albany, NY 12203, USA.
Correspondence to: Prof. Yubing Xie, Colleges of Nanoscale Science and Engineering, SUNY Polytechnic Institute, 257 Fuller
Road, Albany, NY 12203, USA. E-mail: YXie@sunypoly.edu
How to cite this article: Mooney B, Tian YI, Rousseau E, Xie Y. Understanding convergent signaling regulation in metastatic
breast cancer cells using a bioengineered stem cell microenvironment. J Cancer Metastasis Treat 2019;5:19.
http://dx.doi.org/10.20517/2394-4722.2018.93

Received: 8 Dec 2018 First Decision: 24 Jan 2019 Revised: 28 Jan 2019 Accepted: 12 Feb 2019 Published: 22 Mar 2019
Science Editor: William P. Schiemann Copy Editor: Cai-Hong Wang Production Editor: Huan-Liang Wu

Abstract
Aim: The convergence of tumorigenic and embryonic signaling pathways drives us to exploit the embryonic stem
cell (ESC) microenvironment to restrict metastatic potential of cancer cells. We have previously demonstrated
that bioengineered ESC microenvironments could restrict growth and metastatic potential of highly aggressive
breast cancer cell (BCC). This study aims to further understand the regulation of convergent EGFR and
canonical Wnt/β-catenin signaling pathway function in triple negative metastatic BCCs using the 3D in vitro ESC
microenvironment created by encapsulating ESCs in alginate hydrogel microstrands.

Methods: Co-culture with ESC-microstrands increased sensitivity to two chemotherapeutic drugs in metastatic
BCCs. To test whether these changes were due to restored signaling pathway regulation in BCCs, we probed for
changes in gene expression of key molecules related to the EGFR and canonical Wnt/β-catenin signaling pathways
using quantitative reverse transcription polymerase chain reaction and Western blot analysis.

Results: ESC-microstrands are able to alter the gene expression of highly aggressive BCCs at both mRNA and
protein levels. These changes are indicative of a reversal of EGFR and canonical Wnt/β-catenin signaling pathway
hyperactivation following co-culture. Increased NKD2 mRNA and protein expression coinciding with dual signaling
pathway inhibition within co-cultured BCCs suggests that this reversal may be attributable to restored regulation
of NKD2 within these pathways.

Conclusion: ESC-microstrands are able to reverse oncogenic signaling pathway hyperactivation and restore signaling
pathway regulation in metastatic BCCs. Further studies could provide insight into what role NKD2 up-regulation plays

© The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

www.jcmtjournal.com