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Intussusceptive microvascular growth in human glioma

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Abstract

Intussusceptive microvascular growth (IMG), which occurs by splitting of the existing vasculature by transluminal pillars or transendothelial bridges, has been demonstrated in several tumors such as colon and mammary carcinomas, melanoma and B-cell non-Hodgkin’s lymphomas. In this study, we have correlated in human glioma the extent of angiogenesis, evaluated as microvascular density, the immunoreactivity of tumor cells to vascular endothelial growth factor (VEGF), vessel diameter and IMG to the tumor stage. Results demonstrate for the first time a relationship in human glioma progression between angiogenesis, VEGF immunoreactivity of tumor cells, vessel diameter and the number of connections of intraluminal tissue folds with the opposite vascular wall, expression of IMG and suggest that IMG could be a mechanism of compensatory vascular growth occurring in human glioma. The advantages are that (1) blood vessels are generated more rapidly; (2) it is energetically and metabolically more economic; (3) the capillaries thereby formed are less leaky.

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References

  1. Ribatti D, Vacca A, Dammacco F (1999) The role of the vascular phase in solid tumor growth: a historical review. Neoplasia 1:293–302

    Article  CAS  PubMed  Google Scholar 

  2. Risau W (1997) Mechanism of angiogenesis. Nature 386:671–674

    Article  CAS  PubMed  Google Scholar 

  3. Burri PH, Djonov V (2002) Intussusceptive angiogenesis—the alternative to capillary sprouting. Mol Aspects Med 23:S1–S27

    Article  PubMed  Google Scholar 

  4. Burri PH, Tarek MR (1990) A novel mechanism of capillary growth in the rat pulmonary microcirculation. Anat Rec 228:35–45

    Article  CAS  PubMed  Google Scholar 

  5. van Groningen JP, Wenink AC, Testers LH (1991) Myocardial capillaries: increase in number by splitting of existing vessels. Anat Embryol 184:65–70

    Article  PubMed  Google Scholar 

  6. Patan S, Haenni B, Burri PH (1993) Evidence for intussusceptive capillary growth in the chicken chorio-allantoic membrane (CAM). Anat Embryol 187:121–130

    Article  CAS  PubMed  Google Scholar 

  7. Crivellato E, Nico B, Vacca A, Djonov V, Presta M, Ribatti D (2004) Recombinant human erythropoietin induces intussusceptive microvascular growth in vivo. Leukemia 18:331–336

    Article  CAS  PubMed  Google Scholar 

  8. Patan S, Munn LL, Jain RK (1996) Intussusceptive microvascular growth in a human colon adenocarcinoma xenograft: a novel mechanism of tumor angiogenesis. Microvasc Res 51:260–272

    Article  CAS  PubMed  Google Scholar 

  9. Djonov V, Andres AC, Ziemiecki A (2001) Vascular remodeling during the normal and malignant life cycle of the mammary gland. Microsc Res Tech 52:182–189

    Article  CAS  PubMed  Google Scholar 

  10. Crivellato E, Nico B, Vacca A, Ribatti D (2003) B-cell non-Hodgkin’s lymphomas express heterogeneous patterns of neovascularization. Haematologica 88:671–678

    PubMed  Google Scholar 

  11. Ribatti D, Nico B, Floris C et al (2005) Microvascular density, vascular endothelial growth factor immunoreactivity in tumor cells, vessel diameter and intussusceptive microvascular growth in primary melanoma. Oncol Rep 14:81–84

    PubMed  Google Scholar 

  12. Kleihues P, Cavanee WK (2000) Astrocytic tumors. In: Kleihues P, Cavanee WK (eds) Pathology and genetics of tumors of the nervous system. World Health Organization Classification of Tumours. ISN Neuropath Press, Basel, Switzerland, pp 9–52

  13. Plate KH, Risau W (1995) Angiogenesis in malignant gliomas. Glia 15:339–347

    Article  CAS  PubMed  Google Scholar 

  14. Machein MR, Plate KH (2000) VEGF in brain tumors. J Neurooncol 50:109–120

    Article  CAS  PubMed  Google Scholar 

  15. Fischer I, Gagner JP, Law M, Newcomb EW, Zagzag D (2005) Angiogenesis in gliomas: biology and molecular pathophysiology. Brain Pathol 15:297–310

    Article  CAS  PubMed  Google Scholar 

  16. Bernsen HJJA, Rijken PFJW, Peters JPW, Bakker H, van der Kogel A (1998) Delayed vascular changes after antiangiogenic therapy with anti-vascular endothelial growth factor antibodies in human glioma xenografts in nude mice. Neurosurgery 43:570–575

    Article  CAS  PubMed  Google Scholar 

  17. Rubenstein JL, Kim J, Ozawa T et al (2000) Anti-VEGF antibody treatment of glioblastoma prolongs survival but results in increased vascular cooption. Neoplasia 2:306–314

    Article  CAS  PubMed  Google Scholar 

  18. Ribatti D, Nico B, Crivellato E, Vacca A (2007) The structure of the vascular network of tumors. Cancer Lett 248:18–23

    Article  CAS  PubMed  Google Scholar 

  19. Sundbrg C, Nagy JA, Brown LF et al (2001) Glomeruloid microvascular proliferation follows adenoviral vascular permeability factor/vascular endothelial growth factor-164 gene delivery. Am J Pathol 158:1145–1160

    Google Scholar 

  20. Kleihues P, Burger PC, Scheithauer BW (1993) The new WHO classification of brain tumours. Brain Pathol 3:255–268

    Article  CAS  PubMed  Google Scholar 

  21. Elias H, Hyde DM (1983) Stereological measurements of isotropic structures. In: Elias H, Hyde DM (eds) A guide to practical stereology. Basel, Karger, pp 22–44

    Google Scholar 

  22. Guidolin D, Zunarelli E, Genedani S, Trentini GP, De Gaetani C, Fuxe K, Benegiamo C, Agnati LF (2008) Opposite patterns of age-associated changes in neurons and glial cells of the thalamus of human brain. Neurobiol Aging 29:926–936

    Article  CAS  PubMed  Google Scholar 

  23. Semela D, Piguet AC, Kolev M et al (2007) Vascular remodeling and antitumoral effects of mTOR inhibition in a rat model of hepatocellular carcinoma. J Hepatol 46:840–848

    Article  CAS  PubMed  Google Scholar 

  24. Hlushchuk R, Riesterer O, Baum O et al (2008) Tumor recovery by angiogenic switch from sprouting to intussusceptive angiogenesis after treatment with PTK787/ZK222584 or ionizing radiation. Am J Pathol 173:1173–1185

    Article  CAS  PubMed  Google Scholar 

  25. Kurz H, Burri PH, Djonov V (2003) Angiogenesis and vascular remodeling by intussusception: form to function. News Physiol Sci 18:65–70

    PubMed  Google Scholar 

  26. Drake CJ, Little CD (1999) VEGF and vascular fusion: implications for normal and pathological vessels. J Histochem Cytochem 74:1351–1355

    Google Scholar 

  27. Nakatsu MN, Sainson RC, Perez-del-Pulgar S et al (2003) VEGF (121) and VEGF (165) regulate blood vessel diameter through vascular endothelial growth factor receptor-2 in an in vitro angiogenesis model. Lab Invest 83:1873–1885

    Article  CAS  PubMed  Google Scholar 

  28. Breier G, Risau W (1996) Angiogenesis in the developing brain and brain tumors. Trends Exp Med 6:362–376

    Google Scholar 

  29. Drake CJ, Little CD (1995) Exogenous vascular endothelial growth factor induces malformed and hyperfused vessels during embryonic neovascularization. Proc Natl Acad Sci USA 92:7657–7661

    Article  CAS  PubMed  Google Scholar 

  30. Makanya AN, Hlushchuk R, Djonov V (2009) Intussusceptive angiogenesis and its role in vascular morphogenesis, patterning, and remodeling. Angiogenesis 12:113–123

    Article  CAS  PubMed  Google Scholar 

  31. Thurston G (2002) Complementary actions of VEGF and angiopoietin-1 on blood vessel growth and leakage. J Anat 200:575–580

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by the Ministry for Education, the Universities and Research (PRIN 2007), Rome, Italy and Fondazione Cassa di Risparmio di Puglia, Bari, Italy.

Conflict of interest statement

The authors declare that they have no conflict of interest related to the publication of this manuscript.

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Authors and Affiliations

  1. Department of Human Anatomy and Histology, University of Bari Medical School, Piazza G. Cesare, 11, Policlinico, 70124, Bari, Italy

    Beatrice Nico, Tiziana Annese & Domenico Ribatti

  2. Department of Medical and Morphological Research, Section of Anatomy, University of Udine Medical School, Udine, Italy

    Enrico Crivellato

  3. Department of Human Anatomy and Physiology, Section of Anatomy, University of Padua Medical School, Padua, Italy

    Diego Guidolin

  4. Department of Internal Medicine and Clinical Oncology, University of Bari Medical School, Bari, Italy

    Vito Longo & Angelo Vacca

  5. Department of Medical and Morphological Research, Section of Pathology, University of Udine Medical School, Udine, Italy

    Nicoletta Finato

Authors
  1. Beatrice Nico
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  2. Enrico Crivellato
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  3. Diego Guidolin
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  4. Tiziana Annese
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  5. Vito Longo
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  6. Nicoletta Finato
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  7. Angelo Vacca
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  8. Domenico Ribatti
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Correspondence to Domenico Ribatti.

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Nico, B., Crivellato, E., Guidolin, D. et al. Intussusceptive microvascular growth in human glioma. Clin Exp Med 10, 93–98 (2010). https://doi.org/10.1007/s10238-009-0076-7

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  • DOI: https://doi.org/10.1007/s10238-009-0076-7

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