Human Umbilical Cord Matrix Mesenchymal Stem Cells Suppress the Growth of Breast Cancer by Expression of Tumor Suppressor Genes

Abstract

Human and rat umbilical cord matrix mesenchymal stem cells (UCMSC) possess the ability to control the growth of breast carcinoma cells. Comparative analyses of two types of UCMSC suggest that rat UCMSC-dependent growth regulation is significantly stronger than that of human UCMSC. Their different tumoricidal abilities were clarified by analyzing gene expression profiles in the two types of UCMSC. Microarray analysis revealed differential gene expression between untreated naïve UCMSC and those co-cultured with species-matched breast carcinoma cells. The analyses screened 17 differentially expressed genes that are commonly detected in both human and rat UCMSC. The comparison between the two sets of gene expression profiles identified two tumor suppressor genes, adipose-differentiation related protein (ADRP) and follistatin (FST), that were specifically up-regulated in rat UCMSC, but down-regulated in human UCMSC when they were co-cultured with the corresponding species’ breast carcinoma cells. Over-expression of FST, but not ADRP, in human UCMSC enhanced their ability to suppress the growth of MDA-231 cells. The growth of MDA-231 cells was also significantly lower when they were cultured in medium conditioned with FST, but not ADRP over-expressing human UCMSC. In the breast carcinoma lung metastasis model generated with MDA-231 cells, systemic treatment with FST-over-expressing human UCMSC significantly attenuated the tumor burden. These results suggest that FST may play an important role in exhibiting stronger tumoricidal ability in rat UCMSC than human UCMSC and also implies that human UCMSC can be transformed into stronger tumoricidal cells by enhancing tumor suppressor gene expression.

Cell Wall Membrane Fraction of Chlorella sorokiniana Enhances Host Antitumor Immunity and Inhibits Colon Carcinoma Growth in Mice

“…It is known that growth of cancer cells under 3D culture mimics tumor growth in vivo more than that under 2D culture conditions. 16 For this reason, 3D culture methods such as spheroid assays 16,17,[30][31][32][33] have been applied for the evaluation and screening of novel therapeutics for cancer treatments. In the present study, CMF treatment alone attenuated the growth of CT26 cells in both 2D culture ( Figure 2A) and a spheroid assay (Figure 3A and B).…”

Exopolysaccharides extracted from Parachlorella kessleri inhibit colon carcinoma growth in mice via stimulation of host antitumor immune responses

“…It is known that 3D culture condition more closely mimics natural tumor growth than that in 2D culture condition [34]. For this reason, 3D culture methods such as clonogenic assay [42–44] and spheroid assay [34] have been applied to the evaluation and screening of novel therapeutics for cancer treatments. Present study results, therefore, may suggest that the cytotoxic antitumor effect of PCEPS alone is not strong enough to inhibit 3D spheroid growth of CT26 cells within a short time.…”

Inhibition of breast tumor growth and abnormal angiogenesis in mice treated with endothelial cells and their progenitor mesenchymal stem cells derived from bone marrow

“…I.V administration of MSCs can effectively inhibit tumor cell proliferation and inhibition of metastasis [19]. Also, it was reported that the MSCs isolated from human and rat umbilical cord could significantly suppress growth of breast cancer cells in vitro and in vivo [43][44][45].…”