J Cancer 2019; 10(19):4532-4539. doi:10.7150/jca.30788

Research Paper

Mesenchymal Stem Cells Accelerate the Remodeling of Bladder VX2 Tumor Interstitial Microenvironment by TGFβ1-Smad Pathway

Qingya Yang1, Jun Chen1,2✉, Yaofeng Zhu2, Zhishun Xu2

1. Department of Urology, Qilu Hospital (Qingdao), Shandong University, Qingdao 266035, China.
2. Department of Urology, Qilu Hospital, Shandong University, Jinan 250012, China

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Citation:
Yang Q, Chen J, Zhu Y, Xu Z. Mesenchymal Stem Cells Accelerate the Remodeling of Bladder VX2 Tumor Interstitial Microenvironment by TGFβ1-Smad Pathway. J Cancer 2019; 10(19):4532-4539. doi:10.7150/jca.30788. Available from http://www.jcancer.org/v10p4532.htm

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Abstract

Background: Mesenchymal stem cells (MSCs) have been proved to be able to differentiate into cells that are conducive to tumor growth and invasion. The mechanism is not clear. This present study was aimed to find out whether TGFβ1-Smad pathway was involved in this process.

Methods: For the in vitro experiment, five groups of MSCs were cultured to test whether VX2 culture supernatant could induce the differentiation of MSCs into myofibroblasts. And then transforming growth factor β1(TGFβ1) receptor or Smad2 of MSCs were blocked by RNA interference technique to test whether TGFβ1-Smad pathway was involved in the differentiation. In the animal experiment, different kinds of MSCs were co-inoculated with VX2 cells in bladder to test whether the blockage of TGFβ1 receptor or Smad2 of MSCs could affect the expression of TGFβ1, epidermal growth factor (EGF), fibroblast activation protein alpha (FAPa), and matrix metalloprotein 9 (MMP9) in five animal groups.

Results: VX2 culture supernatant could up-regulate the expression of α-SMA and Vimentin in MSCs, which indicated that VX2 culture supernatant could induce the differentiation of MSCs into myofibroblasts. Either the Blockage of TGFβ1 receptor or Smad2 of MSCs could lead to decreased expression of α-SMA and Vimentin in MSCs. In the animal experiment, MSCs could favor VX2 bladder tumor growth and up-regulate the expression of TGFβ1, EGF, FAPa, MMP9 in VX2 tumor tissue. However, when TGFβ1 receptor or Smad2 of MSCs was blocked, the above effects were attenuated.

Conclusions: Under the induction of tumor microenvironment, MSCs can differentiate into myofibroblasts and then affect tumor interstitial microenvironment remodeling. This process is mediated by TGFβ1-Smad2 pathway.

Keywords: Mesenchymal stem cells, tumor, stroma remodeling