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.
Highlights
The epithelial ovarian cancer (EOC) is still the most deadly gynaecological tumour [1] because of late detection, local recurrence, and metastasis
The adipose-derived mesenchymal stem cells (ADSCs) conditioned medium (CM)-treated ovarian cancer cells exhibited significantly increased proliferation compared with cancer cells
Based on the results of the scratchwound assays, ADSC CM increased the number of migrating cancer cells after 24 h; the migrated SKOV3 number, HO8910 cells, and ES2 cells treated with CM increased by 53.0%, 67.5%, and 54.2%, respectively, compared with the number of migrated cells cultured with normal medium (P < 0:001)
Summary
The epithelial ovarian cancer (EOC) is still the most deadly gynaecological tumour [1] because of late detection, local recurrence, and metastasis. The underlying mechanisms of omental metastasis in ovarian cancer are complex and ambiguous. Studies examining this topic are very important for the treatment of ovarian cancer. The TME has been reported to have significant contributions to the metastasis of ovarian cancer [4, 5]. By using ADSCs in the omentum, the growth and invasion of ovarian cancer were increased significantly, indicating that the ovarian cancer progression is promoted [6]. The prometastatic TME in the omentum that promotes omental metastasis is formed during this process; the underlying mechanism is not entirely understood
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