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

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.

In Vitro Cultures of Adipose-Derived Stem Cells: An Overview of Methods, Molecular Analyses, and Clinical Applications

“…Therefore, ASCs affect the growth and metastasis of ovarian cancer, but underlying mechanisms have not been fully understood yet. However, the protein expression of ovarian cancers cells has been compared with protein expression following treatment ASCs, revealing that thymosin beta 4 X-linked (TMSB4X) accelerated ASC-mediated proliferation, invasion, and migration of ovarian cancer cells [52].…”

Adipose-Derived Mesenchymal Stem Cells do not Affect the Invasion and Migration Potential of Oral Squamous Carcinoma Cells

“…In recent decades, the role of MSCs in cancer has generated interest and several studies have been carried out to that end, but the results have been controversial. Some studies attribute both AT-MSCs and BM-MSCs to promoting tumor progression and metastasis [6,8,9]. Cells co-expressing MSC markers CD73, CD90 and CD105 were reported to be enriched in head and neck squamous cell carcinoma [10].…”

<p>Adipose-Derived Stem Cells Promote Proliferation and Invasion in Cervical Cancer by Targeting the HGF/c-MET Pathway</p>

“…16 For example, Wang reported that ADSCs could enhance ovarian cancer growth and metastasis by increasing thymosin beta 4x-linked expression. 17 It was also reported that ADSCs could attenuate the cisplatininduced apoptosis in ovarian cancer cells, serving as a therapeutic method. 18 On the other hand, Takahara showed that ADSCs inhibited prostate cancer cell proliferation by inducing apoptosis.…”