Open AccessMesenchymal Stem/Stromal Cell Engulfment Reveals Metastatic Advantage in Breast Cancer
Author(s) -
YuChih Chen,
María E. González,
Boris Burman,
Xintao Zhao,
Talha Anwar,
Mai Tran,
Natasha Medhora,
Ayse Buke Hiziroglu,
Wonchoel Lee,
Yu-Heng Cheng,
Yehyun Choi,
Euisik Yoon,
Celina G. Kleer
Publication year - 2019
Publication title -
cell reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.264
H-Index - 154
eISSN - 2639-1856
pISSN - 2211-1247
DOI - 10.1016/j.celrep.2019.05.084
Subject(s) - mesenchymal stem cell , metastasis , stromal cell , cancer research , tumor microenvironment , cancer stem cell , biology , stem cell , flow cytometry , cancer cell , breast cancer , cell , cancer , microbiology and biotechnology , immunology , tumor cells , genetics
Twenty percent of breast cancer (BC) patients develop distant metastasis for which there is no cure. Mesenchymal stem/stromal cells (MSCs) in the tumor microenvironment were shown to stimulate metastasis, but the mechanisms are unclear. Here, we identified and quantified cancer cells engulfing stromal cells in clinical samples of BC metastasis by dual immunostaining for EZH2 and ALDH1 expression. Using flow cytometry and a microfluidic single-cell paring and retrieval platform, we show that MSC engulfment capacity is associated with BC cell metastatic potential and generates cells with mesenchymal-like, invasion, and stem cell traits. Whole-transcriptome analyses of selectively retrieved engulfing BC cells identify a gene signature of MSC engulfment consisting of WNT5A, MSR1, ELMO1, IL1RL2, ZPLD1, and SIRPB1. These results delineate a mechanism by which MSCs in the tumor microenvironment promote metastasis and provide a microfluidic platform with the potential to predict BC metastasis in clinical samples.
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