Advertisement

Glioma stem cells reconstruct similar immunoinflammatory microenvironment in different transplant sites and induce malignant transformation of tumor microenvironment cells

  • Tao Xie
  • Bing Liu
  • Chun-Gang Dai
  • Zhao-Hui Lu
  • Jun Dong
  • Qiang Huang
Original Article – Cancer Research

Abstract

Purpose

This study aimed to examine whether the different tumor-transplanted sites could construct a similar immunoinflammatory microenvironment and to investigate the interactions between tumor microenvironment cells.

Methods

The red fluorescent protein-SU3 (SU3-RFP) or SU3 glioma stem cells (GSC) were inoculated into the brain, liver, abdominal cavity, and subcutis of green fluorescent protein (GFP)-nude mice. The tumor tissues were taken to observe the tissue cell distribution. The single cell suspension of tumor tissues was prepared and cultured, while the SU3-RFP cells were co-cultured with the cells from GFP-transgenic mice. The RFP+, GFP+, and RFP+/GFP+ cells were traced by fluorescence microscope, and their protein expressions were determined by Western blot analysis. The markers of immunoinflammatory cells, including F4/80, CD11b, CD11c, CD80, CD47, and SIRP-α, were determined by RT-PCR and immunocytochemistry assays, respectively.

Results

The xenograft models of all transplant sites were inducible, and the red tumor cells of tumor tissues were encircled by a great quantity of host-derived green cells, including immunoinflammatory cells with CD80, F4/80, CD11b, and CD11c expressions, which might generate the cell colonies and possess the pseudopodia. Additionally, the interactions between red tumor cells and green immunoinflammatory cells, including cell fusion process and yellow fusion cell formation, were observed in cultured cells. The fusion cells-derived B4 cells with expressions of CD47 and SIRP-α proteins had the strong proliferation ability and tumorigenic effect.

Conclusions

The similar tumor immunoinflammatory microenvironment was constructed by GSC in different transplant sites, and the cell fusion indicated a malignant transformation of the tumor microenvironment cells.

Keywords

Glioma stem cells Transplantation tumor model Tumor immunoinflammatory microenvironment Malignant transformation of microenvironment cells 

Abbreviations

GSC

Glioma stem cells

GFP

Green fluorescent protein

RFP

Red fluorescent protein

RT-PCR

Reverse transcription polymerase chain reaction

Sca-1

Stem/progenitor cell surface antigen-1

Notes

Acknowledgements

This work was supported by the National Natural Science Foundation of China (no. 81472739), Science & Technology Project for Medical Health of Suzhou New District (no. 2017Q011), and Suzhou Science & Technology Development Project (no. SYS201507).

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Ethical approval

All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

Informed consent

Informed consent was obtained from all individual participants included in the study.

References

  1. Alvarez-Dolado M, Pardal R, Garcia-Verdugo JM et al (2003) Fusion of bone-marrow-derived cells with Purkinje neurons, cardiomyocytes and hepatocytes. Nature 425:968–973CrossRefGoogle Scholar
  2. Bettinger I, Thanos S, Paulus W (2002) Microglia promote glioma migration. Acta Neuropathol 103:351–355CrossRefGoogle Scholar
  3. Charles NA, Holland EC, Gilbertson R, Glass R, Kettenmann H (2011) The brain tumor microenvironment. Glia 59:1169–1180CrossRefGoogle Scholar
  4. Chen R, Xue J, Xie ML (2011) Reduction of isoprenaline induced myocardial TGF-β1 expression and fibrosis in osthole-treated mice. Toxicol Appl Pharmacol 256:168–173CrossRefGoogle Scholar
  5. Dai X, Chen H, Chen Y et al (2015) Malignant transformation of host stromal fibroblasts derived from the bone marrow traced in a dual-color fluorescence xenograft tumor model. Oncol Rep 34:2997–3006CrossRefGoogle Scholar
  6. Dittmar T, Schwitalla S, Seidel J et al (2011) Characterization of hybrid cells derived from spontaneous fusion events between breast epithelial cells exhibiting stem-like characteristics and breast cancer cells. Clin Exp Metastasis 28:75–90CrossRefGoogle Scholar
  7. Dong J, Zhang QB, Huang Q et al (2010) Glioma stem cells involved in tumor tissue remodeling in a xenograft model. J Neurosurg 113:249–260CrossRefGoogle Scholar
  8. Dong J, Zhao YD, Huang Q et al (2011) Glioma stem/progenitor cells contribute to neovascularization via transdifferentiation. Stem Cell Rev Rep 7:141–152CrossRefGoogle Scholar
  9. Dong J, Dai XL, Lu ZH et al (2012) Incubation and application of transgenic green fluorescent nude mice in visualization studies on glioma tissue remodeling. Chin Med J 125:4349–4354PubMedGoogle Scholar
  10. Duelli D, Lazebnik Y (2007) Cell-to-cell fusion as a link between viruses and cancer. Nat Rev Cancer 7:968–976CrossRefGoogle Scholar
  11. Hanisch UK, Kettenmann H (2007) Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat Neurosci 10:1387–1394CrossRefGoogle Scholar
  12. Kim D, Wang J, Willingham SB, Martin R, Wernig G, Weissman IL (2012) Anti-CD47 antibodies promote phagocytosis and inhibit the growth of human myeloma cells. Leukemia 26:2538–2545CrossRefGoogle Scholar
  13. Lu X, Kang YB (2009) Cell fusion as a hidden force in tumor progression. Cancer Res 69:8536–8539CrossRefGoogle Scholar
  14. Lu X, Kang YB (2011) Cell fusion hypothesis of the cancer stem cell. Adv Exp Med Biol 714:129–140CrossRefGoogle Scholar
  15. Lu ZH, Lv K, Zhang JS et al (2014) Establishment of a green fluorescent protein tracing murine model focused on the functions of host components in necrosis repair and the niche of subcutaneously implanted glioma. Oncol Rep 31:657–664CrossRefGoogle Scholar
  16. Overholtzer M, Mailleux AA, Mouneimneet G et al (2007) A nonapoptotic cell death process, entosis, that occurs by cell-in-cell invasion. Cell 131:966–979CrossRefGoogle Scholar
  17. Pawelek JM (2005) Tumour-cell fusion as a source of myeloid traits in cancer. Lancet Oncol 6:988–993CrossRefGoogle Scholar
  18. Sheehy PF, Wakonigv T, Winn R, Clarkson BD (1974) Asynchronous DNA synthesis and asynchronous mitosis in multinuclear ovarian cancer cells. Cancer Res 34:991–996PubMedGoogle Scholar
  19. Shen YT, Zhang QB, Zhang JS et al (2015) Advantages of a dual-color fluorescence-tracing glioma. orthotopic implantation model: detecting tumor location, angiogenesis, cellular fusion and the tumor microenvironment. Exp Ther Med 10:2047–2054CrossRefGoogle Scholar
  20. Sun C, Zhao DL, Dai XL et al (2015) Fusion of cancer stem cells and mesenchymal stem cells contributes to glioma neovascularization. Oncol Rep 34:2022–2030CrossRefGoogle Scholar
  21. Sun X, Bao J, Shao Y (2016) Mathematical modeling of therapy-induced cancer drug resistance: connecting cancer mechanisms to population survival rates. Sci Rep 6:22498CrossRefGoogle Scholar
  22. Wan Y, Fei XF, Wang ZM et al (2012) Expression of miR-125b in the new, highly invasive glioma stem cell and progenitor cell line SU3. Chin J Cancer 31:207–214CrossRefGoogle Scholar
  23. Wang XY, Xue J, Yang J, Xie ML (2013) Timed high-fat diet in the evening affects the hepatic circadian clock and PPARα-mediated lipogenic gene expressions in mice. Genes Nutr 8:457–463CrossRefGoogle Scholar
  24. Wang AD, Dai XL, Cui BQ et al (2015) Experimental research of host macrophage canceration induced by glioma stem progenitor cells. Mol Med Rep 11:2435–2442CrossRefGoogle Scholar
  25. Watters JJ, Schartner JM, Badie B (2005) Microglia function in brain tumors. J Neurosci Res 81:447–455CrossRefGoogle Scholar
  26. Zhao X, Xue J, Wang XL, Zhang Y, Deng M, Xie ML (2014) Involvement of hepatic peroxisome proliferator-activated receptor α/γ in the therapeutic effect of osthole on high-fat and high-sucrose-induced steatohepatitis in rats. Int Immunopharmacol 22:176–181CrossRefGoogle Scholar
  27. Zheng Y, Bao J, Zhao Q, Zhou T, Sun X (2018) A spatio-temporal model of macrophage-mediated drug resistance in glioma immunotherapy. Mol Cancer Ther 17:814–824CrossRefGoogle Scholar
  28. Zhu YD, Dai XL, Zhao DL, Sun C, Dong J, Huang Q (2013) The effect of glioma stem/progenitor cell on tumor angiogenesis traced by red/green fluorescent protein. Chin J Exp Surg 30:297–299Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.The Experimental Center, Department of NeurosurgeryThe Second Affiliated Hospital of Soochow UniversitySuzhouChina

Personalised recommendations