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. 2019 Oct 20:2019:9037197.
doi: 10.1155/2019/9037197. eCollection 2019.

Adipose-Derived Mesenchymal Stem Cells Enhance Ovarian Cancer Growth and Metastasis by Increasing Thymosin Beta 4X-Linked Expression

Yijing Chu  1 , Min You  1 , Jingjing Zhang  1 , Guoqiang Gao  1 , Rendong Han  1 , Wenqiang Luo  1 , Tingting Liu  1 , Jianxin Zuo  1 , Fuling Wang  1
Affiliations

Adipose-Derived Mesenchymal Stem Cells Enhance Ovarian Cancer Growth and Metastasis by Increasing Thymosin Beta 4X-Linked Expression

Yijing Chu et al. Stem Cells Int. .

Abstract

As shown in our previous studies, growth and metastasis of ovarian cancer can be regulated by adipose-derived mesenchymal stem cells (ADSCs). However, the underlying mechanism has not yet been revealed. In this study, a proteomics analysis was performed to compare protein expression treated with and without ADSCs in ovarian cancer cells. Protein levels were altered in ovarian cancer cells due to the treatment of ADSCs. Thymosin beta 4 X-linked (TMSB4X) levels changed dramatically, and this protein was identified as one of the most important candidate molecules contributing to the tumour-promoting effects of ADSCs. Compared with the cells that are cultured in the normal growth medium, the TMSB4X levels cultured in ADSC-conditioned medium increased significantly in ovarian cancer cells. Furthermore, the growth and invasion of cancer cells were decreased, even in the ADSC-conditioned medium treatment group (P < 0.05), by the inhibition of TMSB4X. As shown in the bioluminescence images captured in vivo, increased ovarian cancer's growth and metastasis, along with elevated TMSB4X expression, were observed in the group of ADSC-conditioned medium, and the tumour-promoting effect of ADSCs was attenuated by the inhibition of TMSB4X. Based on our findings, increased TMSB4X expression may play a role in accelerating the ADSC-mediated proliferation, invasion, and migration of ovarian cancers.

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
ADSCs promote the proliferation, migration, and invasion of ovarian cancer cells in vitro. (a) Representative results of CCK-8 assays in SKOV3, HO8910, and ES2 cells are shown. Cancer cells were treated with ADSC CM. (b) Representative results of scratch-wound assays for the detection of ovarian cancer cell mobility (scale bar, 100 μm). (c) Representative results of Transwell assays in ovarian cancer cells are shown. The number of cancer cells that migrated through the 8 μm Transwell membrane pores was counted to determine changes in the invasive capabilities in response to ADSC CM (scale bar, 50 μm).
Figure 2
Figure 2
ADSC increases the expression of TMSB4X in ovarian cancer cells, and the expression levels of TMSB4X in shRNA-transfected ovarian cancer cells are decreased. (a) Cancer cells were transfected with TMSB4X shRNA or shNC. TMSB4X expression was detected in three lines of transfected ovarian cancer cells cultured alone or with ADSC CM by western blot. (b) The histograms show the quantification of the relative expression of TMSB4X. (c) Significant increases in TMSB4X mRNA were found in SKOV3, HO8910, and ES2 cells treated with ADSC CM by qRT-PCR. The results are expressed as the means ± SD.
Figure 3
Figure 3
ADSCs enhance the proliferation, migration, and invasion of ovarian cancer cells by increasing TMSB4X expression in vitro. (a) Cell proliferation was evaluated by a CCK-8 assay. Three ovarian cancer cell lines transfected with TMSB4X shRNA were treated with ADSC CM. Ovarian cancer cells transfected with shNC/lipo2000 and treated with ADSC CM served as the positive control, and cancer cells transfected with TMSB4X shRNA and cultured in normal growth medium served as the negative control. (b) Representative results of scratch-wound assays for ovarian cancer cell migration abilities. (c) Cancer cell invasion abilities were determined by Transwell assay (scale bar, 50 μm). ∗∗∗P < 0.001.
Figure 4
Figure 4
ADSCs enhance the proliferation, migration, and invasion of ovarian cancer cells by increasing TMSB4X expression in nude mouse models. (a) An in vivo imaging system was used to monitor SKOV3 xenograft luminescence activity, which represented tumour growth and metastasis. (b) Living Image software was used to analyse tumour bioluminescence intensity weekly. Quantitative results regarding the normalized image counts are shown. (c) Immunohistochemical analysis results regarding Ki67 and TMSB4X expression in the orthotopic tumour xenografts are shown. Quantitative results of Ki67 and TMSB4X expression-positive area in xenografts on the right panel. ∗P < 0.05, ∗∗P < 0.01, and ∗∗∗P < 0.001.
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