Oncotarget

Research Papers:

CD109 released from human bone marrow mesenchymal stem cells attenuates TGF-β-induced epithelial to mesenchymal transition and stemness of squamous cell carcinoma

Shufeng Zhou, Renzo Cecere and Anie Philip _

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2017; 8:95632-95647. https://doi.org/10.18632/oncotarget.21067

Metrics: PDF 608 views  |   HTML 972 views  |   ?  


Abstract

Shufeng Zhou1, Renzo Cecere2 and Anie Philip1

1Division of Plastic Surgery, Department of Surgery, McGill University, Montreal, QC, Canada

2Division of Cardiac Surgery, Department of Surgery, McGill University, Montreal, QC, Canada

Correspondence to:

Anie Philip, email: anie.philip@mcgill.ca

Keywords: human bone marrow mesenchymal stem cells; squamous cell carcinoma; CD109; TGF-β; epithelial to mesenchymal transition

Abbreviations: hBM-MSC-CM: human bone marrow mesenchymal stem cells conditioned medium; hFibro-CM: human fibroblast cells conditioned medium; EMT: epithelial to mesenchymal transition; SCC: squamous cell carcinoma

Received: March 31, 2017     Accepted: July 06, 2017     Published: September 16, 2017

ABSTRACT

Although there is increasing evidence that human bone marrow mesenchymal stem cells (hBM-MSCs) play an important role in cancer progression, the underlying mechanisms are poorly understood. Transforming growth factor β (TGF-β) is an important pro-metastatic cytokine. We have previously shown that CD109, a glycosylphosphatidylinositol-anchored protein, is a TGF-β co-receptor and a strong inhibitor of TGF-β signalling. Moreover, CD109 can be released from the cell surface. In the current study, we examined whether hBM-MSCs regulate the malignant properties of squamous cell carcinoma cells, and whether CD109 plays a role in mediating the effect of hBM-MSCs on cancer cells. Here we show that hBM-MSC-conditioned medium decreases proliferation and induces apoptosis in human squamous carcinoma cell lines, A431 and FaDu. Importantly, hBM-MSC-conditioned medium markedly suppresses markers of epithelial-to-mesenchymal transition and stemness, and concomitantly decreases cell migration, invasion, and spheroid formation in A431 and FaDu cells. In addition, knockdown of CD109 in hBM-MSCs abrogates the anti-malignant activity of hBM-MSC-conditioned medium on A431 and FaDu cells. Furthermore, overexpression of CD109 in A431 cells decreases their malignant traits. Together, our findings suggest that hBM-MSCs inhibit the malignant traits of squamous cell carcinoma cells by a paracrine effect via released factors and that CD109 released from hBM-MSCs, at least partially, mediates these effects.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 21067