Skip to main content

Advertisement

SpringerLink
Log in

Independent motile microplast formation correlates with glioma cell invasiveness

  • Laboratory Investigation
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Diffuse brain invasion co ntributes to the poor prognosis for patients with gliomas. Analyzing glioma cell migration in vitro, we have demonstrated the spontaneous shedding of anucleate cell fragments that separate from glioma cell bodies and maintain viability from hours to days. Unlike previously described cell fragments that are released from cells as diffusible vectors, glioma cell fragments are independently motile. We used computerized time-lapse microscopy to characterize the formation of these independent motile microplasts (IMMPs) in human cell cultures derived from the most highly invasive glial tumor, glioblastoma. IMMPs were larger than previously described cell fragments, ranging in size from approximately 2% to nearly half of the area of their parent cells. Complex cell-like behaviors—including establishment of polarity, extension of lamellipodia and filopodia, and change in direction of movement—remained intact in IMMPs. The average direction and velocity of the IMMPs were indistinguishable from those of their parent cells. IMMPs formed at a significantly higher rate in glioma cell lines rendered more invasive by overexpression of invasion-related genes than in vector-transfected controls. The correlation with cell invasiveness indicates that IMMP formation may be related to the cell-invasive phenotype. Further investigation will determine whether IMMPs represent a novel addition to the growing list of viable cell fragments with biological relevance.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Johnstone RM (1992) Maturation of reticulocytes: formation of exosomes as a mechanism for shedding membrane proteins. In Proceedings of The Jeanne Manery–Fisher Memorial Lecture 1991. Biochem Cell Biol 70:179–190 Review

    Article  PubMed  CAS  Google Scholar 

  2. Johnstone RM (2005) Revisiting the road to the discovery of exosomes. Blood Cells Mol Dis 34:214–219

    Article  PubMed  CAS  Google Scholar 

  3. Taieb J, Chaput N, Zitvogel L (2005) Dendritic cell-derived exosomes as cell-free peptide-based vaccines. Crit Rev Immunol 25:215–223

    Article  PubMed  CAS  Google Scholar 

  4. Caby MP, Lankar D, Vincendeau-Scherrer C, Raposo G, Bonnerot C (2005) Exosomal-like vesicles are present in human blood plasma. Int Immunol 17:879–887

    Article  PubMed  CAS  Google Scholar 

  5. Fevrier B, Raposo G (2004) Exosomes: endosomal-derived vesicles shipping extracellular messages. Curr Opin Cell Biol 16:415–421

    Article  PubMed  CAS  Google Scholar 

  6. Kramer B, Pelchen-Matthews A, Deneka M, Garcia E, Piguet V, Marsh M (2005) HIV interaction with endosomes in macrophages and dendritic cells. Blood Cells Mol Dis 35:136–142

    Article  PubMed  CAS  Google Scholar 

  7. Porto-Carreiro I, Fevrier B, Paquet S, Vilette D, Raposo G (2005) Prions and exosomes: from PrPc trafficking to PrPsc propagation. Blood Cells Mol Dis 35:143–148

    Article  PubMed  CAS  Google Scholar 

  8. Fevrier B, Vilette D, Laude H, Raposo G (2005) Exosomes: a bubble ride for prions? Traffic 6:10–17

    Article  PubMed  CAS  Google Scholar 

  9. Navabi H, Croston D, Hobot J, Clayton A, Zitvogel L, Jasani B, Bailey-Wood R, Wilson K, Tabi Z, Mason MD, Adams M (2005) Preparation of human ovarian cancer ascites-derived exosomes for a clinical trial. Blood Cells Mol Dis 35:149–152

    Article  PubMed  CAS  Google Scholar 

  10. Couzin J (2005) Cell biology: The ins and outs of exosomes. Science 308:1862–1863 Erratum in: Science. Jul 22; 309: 558, 2005

    Article  PubMed  CAS  Google Scholar 

  11. Andre P, Hartwell D, Hrachovinova I, Saffaripour S, Wagner DD (2000) Pro-coagulant state resulting from high levels of soluble P-selectin in blood. Proc Natl Acad Sci U S A 97:13835–13840

    Article  PubMed  CAS  Google Scholar 

  12. Jimenez JJ, Jy W, Mauro LM, Horstman LL, Bidot CJ, Ahn YS (2005) Endothelial microparticles (EMP) as vascular disease markers. Adv Clin Chem 39:131–157

    PubMed  Google Scholar 

  13. Kim HK, Song KS, Park YS, Kang YH, Lee YJ, Lee KR, Kim HK, Ryu KW, Bae JM, Kim S (2003) Elevated levels of circulating platelet microparticles, VEGF, IL-6 and RANTES in patients with gastric cancer: possible role of a metastasis predictor. Eur J Cancer 39:184–191 Erratum in: Eur J Cancer. Nov; 39: 2569, 2003

    Article  PubMed  CAS  Google Scholar 

  14. Freyssinet JM (2003) Cellular microparticles: what are they bad or good for? J Thromb Haemost 1:1655–1662

    Article  PubMed  CAS  Google Scholar 

  15. Carlsson L, Nilsson O, Larsson A, Stridsberg M, Sahlen G, Ronquist G (2003) Characteristics of human prostasomes isolated from three different sources. Prostate 54:322–330

    Article  PubMed  CAS  Google Scholar 

  16. Kravets FG, Lee J, Singh B, Trocchia A, Pentyala SN, Khan SA (2000) Prostasomes: current concepts. Prostate 43:169–174

    Article  PubMed  CAS  Google Scholar 

  17. Albrecht-Buehler G (1980) Autonomous movements of cytoplasmic fragments. Proc Natl Acad Sci U S A 77:6639–6643

    Article  PubMed  CAS  Google Scholar 

  18. Keller HU, Bessis M (1975) Migration and chemotaxis of anucleate cytoplasmic leukocyte fragments. Nature 258:723–724

    Article  PubMed  CAS  Google Scholar 

  19. Euteneuer U, Schliwa M (1984) Persistent, directional motility of cells and cytoplasmic fragments in the absence of microtubules. Nature 310:58–61

    Article  PubMed  CAS  Google Scholar 

  20. Malawista SE, Van Blaricom G, Chevance de Boisfleury A (1993) Cytokineplasts and U-cytoplasts from human polymorphonuclear leukocytes: role of granule-poor motile fragments in the analysis of cell physiology. Blood Cells 19:63–76 discussion 76–80

    PubMed  CAS  Google Scholar 

  21. Malawista SE, Montgomery RR, Van Blaricom G (1996) Microbial killing by human neutrophil cytokineplasts: similar suppressive effects of reversible and irreversible inhibitors of nitric oxide synthase. J Leukoc Biol 60:753–757

    PubMed  CAS  Google Scholar 

  22. Visted T, Enger PO, Lund-Johansen M, Bjerkvig R (2003) Mechanisms of tumor cell invasion and angiogenesis in the central nervous system. Front Biosci 8:e289–e304

    PubMed  CAS  Google Scholar 

  23. Clatz O, Sermesant M, Bondiau PY, Delingette H, Warfield SK, Malandain G, Ayache N (2005) Realistic simulation of the 3-D growth of brain tumors in MR images coupling diffusion with biomechanical deformation. IEEE Trans Med Imaging 24:1334–1346

    Article  PubMed  Google Scholar 

  24. Sanai N, Alvarez-Buylla A, Berger M (2005) Neural stem cells and the origin of gliomas. N Engl J Med 353:811–822 Review

    Article  PubMed  CAS  Google Scholar 

  25. Oh LYS, Larsen Ph, Krekoshi CA, Edwards DR, Donovan F, Werb Z, Yong VW (1999) Matrix metalloproteinase-9/ Gelatinase B is required for process out growth by oligodendrocytes. J. Neurosc: 19:8464–8475

  26. Berg CP, Engels IH, Rothbart A, Lauber K, Renz A, Schlosser SF, Schulze-Osthoff K, Wesselborg S (2001) Human mature red blood cells express caspase-3 and caspase-8, but are devoid of mitochondrial regulators of apoptosis. Cell Death Differ 8:1197–1206 Comment in: Cell Death Differ 8: 1131–1133, 2001

    Article  PubMed  CAS  Google Scholar 

  27. Jacobson MD, Burne JF, Raff MC (1994) Programmed cell death and Bcl-2 protection in the absence of a nucleus. EMBO J 13:1899–1910

    PubMed  CAS  Google Scholar 

  28. MacKenzie A, Wilson HL, Kiss-Toth E, Dower SK, North RA, Surprenant A (2001) Rapid secretion of interleukin-1beta by microvesicle shedding. Immunity 15:825–835

    Article  PubMed  CAS  Google Scholar 

  29. Hess C, Sadallah S, Hefti A, Landmann R, Schifferli JA (1999) Ectosomes released by human neutrophils are specialized functional units. J Immunol 163:4564–4573

    PubMed  CAS  Google Scholar 

  30. Denis MM, Tolley ND, Bunting M, Schwertz H, Jiang H, Lindemann S, Yost CC, Rubner FJ, Albertine KH, Swoboda KJ, Fratto CM, Tolley E, Kraiss LW, McIntyre TM, Zimmerman GA, Weyrich AS (2005) Escaping the nuclear confines: Signal-dependent pre-mRNA splicing in anucleate platelets. Cell 122:379–391

    Article  PubMed  CAS  Google Scholar 

  31. Kim HK, Song KS, Chung JH, Lee KR, Lee SN (2004) Platelet microparticles induce angiogenesis in vitro. Br J␣Haematol 124:376–384

    Article  PubMed  Google Scholar 

  32. Brill A, Dashevsky O, Rivo J, Gozal Y, Varon D (2005) Platelet-derived microparticles induce angiogenesis and stimulate post-ischemic revascularization. Cardiovasc Res 67:30–38

    Article  PubMed  CAS  Google Scholar 

  33. Hegedus B, Zach J, Czirok A, Lovey Josef, Vicsek T (2004) Irradiation and Taxol treatment result in non-monotonous, dose-dependent changes in the motility of glioblastoma cells. J Neurooncol 67:147–157

    Article  PubMed  Google Scholar 

  34. Abecassis I, Olofsson B, Schmid M, Zalcman G, Karniguian A (2003) RhoA induces MMP-9 expression at CD44 lamellipodial focal complexes and promotes HMEC-1 invasion. Exp Cell Res 291:363–376

    Article  PubMed  CAS  Google Scholar 

  35. Ho CC, Huang PH, Huang HY, Chen YH, Yang PC, Hsu SM (2002) Up-regulated caveolin-1 accentuates the metastatic capability of lung adenocarcinoma by inducing filopodia formation. Am J Pathol 161:1647–1656

    PubMed  CAS  Google Scholar 

  36. Rabinovitz I, Gipson IK, Mercurio AM (2001) Traction forces mediated by alpha6beta4 integrin: implications for basement membrane organization and tumor invasion. Mol Biol Cell 12:4030–4043

    PubMed  CAS  Google Scholar 

  37. Chen WT, Wang JY (1999) Specialized surface protrusions of invasive cells, invadopodia and lamellipodia, have differential MT1-MMP, MMP-2, and TIMP-2 localization. Ann N Y Acad Sci 878:361–371

    Article  PubMed  CAS  Google Scholar 

  38. Elmlinger MW, Deininger MH, Schuett BS, Meyermann R, Duffner F, Grote EH, Ranke MB (2001) In vivo expression of insulin-like growth factor-binding protein-2 in human gliomas increases with the tumor grade. Endocrinology 142:1652–1658

    Article  PubMed  CAS  Google Scholar 

  39. Wang H, Wang H, Shen W, Huang H, Hu L, Ramdas L, Zhou YH, Liao WS, Fuller GN, Zhang W (2003) Insulin-like growth factor binding protein 2 enhances glioblastoma invasion by activating invasion-enhancing genes. Cancer Res 63:4315–4321

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

Authors wish to thank Zach Hall, Caroline Wendell and Brian Wong for technical assistance.

Author information

Author notes

  1. Ryan J. Taft

    Present address: Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia

Authors and Affiliations

  1. California Pacific Medical Center Research Institute, 475 Brannan Street, Suite 220, San Francisco, CA, 94107, USA

    Garret Yount, Ryan J. Taft, Tri Luu, Kenneth Rachlin & Dan Moore

  2. Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA

    Dan Moore

  3. Department of Pathology and Cancer Genomics Core Laboratory, University of Texas, MD Anderson Cancer Center, Houston, TX, USA

    Wei Zhang

Authors
  1. Garret Yount
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ryan J. Taft
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tri Luu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kenneth Rachlin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Dan Moore
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Wei Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Garret Yount.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yount, G., Taft, R.J., Luu, T. et al. Independent motile microplast formation correlates with glioma cell invasiveness. J Neurooncol 81, 113–121 (2007). https://doi.org/10.1007/s11060-006-9211-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-006-9211-4

Keywords

Search

Navigation