Spontaneous formation of tumorigenic hybrids between human omental adipose-derived stromal cells and endometrial cancer cells increased motility and heterogeneity of cancer cells

Cell Cycle. 2019 Feb;18(3):320-332. doi: 10.1080/15384101.2019.1568743. Epub 2019 Jan 22.

Abstract

Recent reports indicate that mesenchymal stem cells (MSCs) can fuse with cancer cells to promote cancer progression. Omental adipose-derived stromal cells (O-ASCs) are similar to MSCs, which could be recruited to the stroma in endometrial cancer. The aim of our study was to investigate whether O-ASCs can fuse with endometrial cancer cells to influence cancer cells biological characteristics. We isolated O-ASCs from patients with endometrial cancer. O-ASCs and endometrial cancer cells were labeled with different fluorescent tags and directly co-cultured in an Opera high-throughput spinning-disk confocal microscopy system to observe the processes involved in the fusion, division and migration of hybrid cells. Immunofluorescence and high-throughput imaging analyzes were performed to evaluate proteins related to epithelial-mesenchymal transition (EMT).We found O-ASCs could spontaneously fuse with endometrial cancer cells, including cytomembrane and nuclear fusion. After fusion, endometrial cancer cells assume an elongated and fibroblast-like appearance that exhibit mesenchymal phenotypes. The hybrid cells proliferated through bipolar and multipolar divisions and exhibited more rapid migratory speeds than were observed in the parental cells (P < 0.01), potentially because of their EMT-associated changes, including the down-regulation of E-cadherin and up-regulation of Vimentin. Our results collectively suggest that tumorigenic hybrids spontaneously formed between human O-ASCs and endometrial cancer cells, and that the resulting cells enhanced cancer mobility and heterogeneity by accelerated migration and undergoing multipolar divisions. These data provide a new avenue for investigating the roles of O-ASCs in endometrial cancer.

Keywords: Cell fusion; EMT; adipose-derived stromal cells; cancer progression; endometrial cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology*
  • Aneuploidy
  • Carcinogenesis
  • Cell Fusion
  • Cell Line, Tumor
  • Cell Movement*
  • Cell Proliferation
  • Endometrial Neoplasms / genetics
  • Endometrial Neoplasms / pathology
  • Endometrial Neoplasms / physiopathology*
  • Epithelial-Mesenchymal Transition
  • Female
  • Humans
  • Hybrid Cells
  • Omentum / cytology
  • Stromal Cells / physiology

Grants and funding

This study was supported by National Key R&D Program of China under Grant 2016YFC1303100.