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During angiogenesis, vascular endothelial growth factor regulate natural killer cell adhesion to tumor endothelium

Nature Medicine volume 2, pages 992–997 (1996)Cite this article

Abstract

Localization of activated natural killer (A–NK) cells in the microvasculature of growing tumors is the result of recognition of the intracellular and vascular cell–adhesion molecules ICAM–1 and VCAM–1 on the tumor endothelium, mediated by lymphocyte function–associated protein LFA–1 and vascular lymphocyte function–associated protein VLA–4. In vitro and in vivo studies of A–NK cell adhesion to endothelial cells showed that vascular endothelial growth factor (VEGF) promotes adhesion, whereas basic fibroblast growth factor (bFGF) inhibits adhesion through the regulation of these molecules on tumor vasculature. Thus, some angiogenic factors may facilitate lymphocyte recognition of angiogenic vessels, whereas others may provide such vessels with a mechanism that protects them from cytotoxic lymphocytes.

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References

  1. Sasaki, A., Melder, R.J., Whiteside, T.L., Herberman, R.B. & Jain, R.K. referential localization of human adherent lymphokine-activated killer cells in tumor microcirculation. J. Natl. Cancer Inst. 53, 433–437 (1991).

    Article  Google Scholar 

  2. Melder, R.J. et al. Imaging of activated natural killer (NK) cells in mice by positron emission tomography (PET): Preferential uptake in tumors. Cancer Res. 53, 5867–5871 (1993).

    CAS  PubMed  Google Scholar 

  3. Melder, R.J., Salehi, H.A. & Jain, R.K. Localization of activated natural killer cells in MCalV mammary carcinoma grown in cranial windows in C3H mice. Microvascular Res. 50, 35–44 (1995).

    Article  CAS  Google Scholar 

  4. Melder, R.J., Walker, E., Herberman, R.B. & Whiteside, T.L. dhesion characteristics of human interleukin 2-activated natural killer cells. Cell. Immunol. 132, 177–192 (1991).

    Article  CAS  Google Scholar 

  5. Allavena, P. et al. Molecules and structures involved in the adhesion of natural killer cells to vascular endothelium. J. Exp. Med. 173, 439–448 (1991).

    Article  CAS  Google Scholar 

  6. Melder, R.J., Munn, L.L., Yamada, S., Ohkubo, C. & Jain, R.K. Selectin- and integrin-mediated T lymphocyte rolling and arrest on TNF-alpha-activated endothelium: Augmentation by erythrocytes. Biophys. J. 69, 2131–2138 (1995).

    Article  CAS  Google Scholar 

  7. Jain, R.K. et al. Leukocyte-endothelial adhesion and angiogenesis in tumors. Cancer Metastasis Rev. 15, 195ndash;204 (1996).

    Article  CAS  Google Scholar 

  8. Munn, L.L., Melder, R.J. & Jain, R.K. Analysis of cell flux in the parallel plate flow chamber: Implications for cell capture studies. Biophys.J. 67, 889–895 (1994).

    Article  CAS  Google Scholar 

  9. Munn, L.L., Koenig, G.C., Jain, R.K. & Melder, R.J. Kinetics of adhesion mole cule expression and spatial organization using targeted sampling fluorometry. BioTechniques 19, 622–631 (1995).

    CAS  PubMed  Google Scholar 

  10. Yuan, F. et al. Vascular permeability and microcirculation of gliomas and mammary carcinomas transplanted in rat and mouse cranial windows. Cancer Res. 54, 4564–4568 (1994).

    CAS  PubMed  Google Scholar 

  11. Jain, R.K. Determinants of tumor blood flow: A review. Cancer Res. 48, 2641 2648 (1988).

    CAS  Google Scholar 

  12. de Fourgerolles, A.R., Stacker, S.A., Schwarting, R. & Springer, T.A. Characterization of ICAM-2 and evidence for a third counter-receptor for LFA-1. Exp.Med 174, 253–267 (1991).

    Article  Google Scholar 

  13. Folkman, J. Tumor angiogenesis. in The Molecular Basis of Cancer (eds. Mendelson, J., Howley, P.M. & Liotta, L.A.) 206–232 (Saunders, Philadelphia, 1995).

    Google Scholar 

  14. Fidler, I.J. & Elis, L.M. The implications of angiogenesis for biology and therapy of cancer metastasis. Cell 79, 185–188 (1994).

    Article  CAS  Google Scholar 

  15. Jallal, B. et al. Suppression of tumor growth in vivo by local and systemic 90K level increase. Cancer Res. 55, 3223–3227 (1995).

    CAS  PubMed  Google Scholar 

  16. Dvorak, H.F., Brown, L.F., Detmar, M. & Dvorak, A.M. ascular permeability factorJvascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am. J. Pathol. 146, 1029–1039 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Reed, J.A., McNutt, N.S. & Albino, A.P. Differential expression of basic FGF (bFGF) in melanocytic lesions demonstrated by in situ hybridization: Implications for tumor progression. Am. J. Pathol. 144, 329–336 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Goto, F., Goto, K., Weidel, K. & Folkman, J. Synergistic effects of vascular endothelial growth factor and basic fibroblast growth factor on the proliferation and cord formation of bovine capillary endothelial cells within collagen gels. J.Lab. Invest. 69, 508–517 (1993).

    CAS  Google Scholar 

  19. Ferrara, N. Missing link in angiogenesis. Nature 376, 467 (1995).

    Article  CAS  Google Scholar 

  20. Koch, A.E., Halloran, M.M., Haskell, C.K., Shah, M.R. & PJ. Angiogenesis mediated by soluble forms of E-selectin and vascular cell adhesion molecule-1. Nature 376, 517–519 (1995).

    Article  CAS  Google Scholar 

  21. Friedlander, M. et al. Definition of two angiogenic pathways by distinct alpha vintegrins. Science 270, 1500–1502 (1995).

    Article  CAS  Google Scholar 

  22. Brooks, P.C. et al. Integrin alpha v beta 3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels. Cell 79, 1157–1164 (1994).

    Article  CAS  Google Scholar 

  23. Fukumura, D. et al. Tumor necrosis factor alpha-induced leukocyte adhesion in normal and tumor vessels: Effect of tumor type, transplantation site, and host strain. Cancer Res. 55, 4824–4829 (1995).

    CAS  PubMed  Google Scholar 

  24. Ohkubo, C., Bigos, D. & Jain, R.K. IL-2 induced leukocyte adhesion to the normal and tumor microvascular endothelium in vivo and its inhibition by dextran sulfate: Implications for vascular- leak syndrome. Cancer Res. 51, 1561 1563 (1991).

    CAS  PubMed  Google Scholar 

  25. Wu, N.Z., Klitzman, B., Dodge, R. & Dewhirst, M.W. iminished leukocyteendothelium interaction in tumor microvessels. Cancer Res. 52, 4265–4268 (1992).

    CAS  PubMed  Google Scholar 

  26. Osborn, L. Leukocyte adhesion to endothelium in inflammation. Cell 62, 3–6 (1990).

    Article  CAS  Google Scholar 

  27. Gamble, J.R., Khew-Goodall, Y. & Vadas, M.A. Transforming growth factor-beta inhibits E-selectin expression on human endothelial cells. J. Immunol. 150, 4494 4503 (1993).

    CAS  PubMed  Google Scholar 

  28. Santambrogio, L. et al. Studies on the mechanisms by which transforming growth factor-beta protects against allergic encephalomyelitis. J. Immunol. 151, 1116–1127 (1993).

    CAS  PubMed  Google Scholar 

  29. Blotnick, S., Peoples, G.E., Freeman, M.R., Eberlein, T.J. & Klagsbrun, M. T lymphocytes synthesize and export heparin-binding epidermal growth factor-like growth factor and basic fibroblast growth factor, mitogens for vascular cells and fibroblasts: Differential production and release by CD4+ and CD8+ T cells. Proc. Natl. Acad. Sci. USA 91, 2890–2894 (1994).

    Article  CAS  Google Scholar 

  30. Freeman, M.R. et al. Peripheral blood T lymphocytes and lymphocytes infiltrating human cancers express vascular endothelial growth factor: A potential role for T cells in angiogenesis. Cancer Res. 55, 4140–4115 (1995).

    CAS  PubMed  Google Scholar 

  31. Dellian, M., Witwer, B.P., Salehi, H.A., Yuan, F. & Jain, R. uantitation and physiological characterization of angiogenic vessels in mice. Am. J. Pathol. 149, 59–71 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Melder, R.J. & Jain, R.K. Kinetics of interleukin-2 induced changes in rigidity of human natural killer cells. Cell Biophys. 20, 161–176 (1992).

    Article  CAS  Google Scholar 

  33. Sasaki, A., Jain, R.K., Maghazachi, A.A., Goldfarb, R.H. & Herberman, R.B. Low deformability of lymphokine-activated killer cells as a possible determinant of in vivo distribution. Cancer Res. 49, 3742–3746 (1989).

    CAS  PubMed  Google Scholar 

  34. Whiteside, T.L. & Goldfarb, R.H. Antitumor effector cells: Extravasation and control of metastasis. Immunol. Ser. 61, 159–173 (1994).

    CAS  PubMed  Google Scholar 

  35. Melder, R.J. et al. Cytotoxic activity against HIV infected monocytes by recombinant interleukin 2-activated natural killer cells. AIDS Res. Hum. Retrovir. 6, 1011–1015 (1990).

    Article  CAS  Google Scholar 

  36. Kitayama, J. et al. Lysis of endothelial cells by autologous lymphokine-activated killer cells. Cancer Immunol. Immunother. 38, 317–322 (1994).

    Article  CAS  Google Scholar 

  37. Watson, C.A., Camera-Benson, L., Palmer-Crocker, R. & Pober, J.S. ariability among human umbilical vein endothelial cultures. Science 268, 447–448 (1995).

    Article  CAS  Google Scholar 

  38. Gullino, P.M. Techniques in tumor pathophysiology. in Methods in Cancer Research (ed. Busch, H.) 45–92 (Academic Press, New York, 1970).

    Google Scholar 

  39. Melder, R.J., Whiteside, T.L., Vujanovic, N.L., Hiserodt, J.C. & Herberman, R.B. A new approach to generating antitumor effectors for adoptive immunotherapy using human adherent lymphokine-activated killer cells. Cancer Res. 48, 3461–3469 (1988).

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital, 100 Fruit Street, Boston, Massachusetts, 02114

    Robert J. Melder, Gerald C. Koenig, Brian P. Witwer, Nina Safabakhsh, Lance L. Munn & Rakesh K. Jain

  2. Harvard Medical School, Boston, Massachusetts, 02114, USA

    Robert J. Melder, Gerald C. Koenig, Brian P. Witwer, Nina Safabakhsh, Lance L. Munn & Rakesh K. Jain

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Melder, R., Koenig, G., Witwer, B. et al. During angiogenesis, vascular endothelial growth factor regulate natural killer cell adhesion to tumor endothelium. Nat Med 2, 992–997 (1996). https://doi.org/10.1038/nm0996-992

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