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
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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: [email protected]
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.
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