Advertisement

Clinical & Experimental Metastasis

, Volume 18, Issue 3, pp 231–237 | Cite as

Persistence of human vascular endothelium in experimental human prostate cancer bone tumors

  • Jeffrey A. Nemeth
  • Jason W. Roberts
  • Chadwick M. Mullins
  • Michael L. Cher
Article

Abstract

Using the SCID-human model, we recently found that human circulating prostate cancer cells formed tumors in human bone but not mouse bone (Nemeth et al. Cancer Res 1999; 59: 1987–93). It is possible that this tissue preference was mediated by interaction between human tumor cells and human endothelial cells within the implanted bone tissue. We sought to determine the relative amounts of human and mouse vasculature within human bone implants and resulting prostate cancer bone tumors in the SCID-human model. Paraffin sections of plain bone implants or PC3 or LNCaP human bone tumors were double stained for factor VIII (all vessels) and human CD31 (human vessels) followed by fluorescent secondary reagents. At 4 weeks post implantation (when cancer cells are typically introduced), the vasculature within human bone fragments remained primarily human (84.5%), and this pattern persisted to at least 10 weeks (91.6% human). Injection of PC3 cells into the bone resulted in an increase in mouse-derived vessels, however the majority (58%) of the vessels remained human even after the formation of large bone tumors. LNCaP bone tumors were highly angiogenic, and there was a sharp decline in the proportion of vessels which were antigenically human (36.8%), suggesting recruitment of mouse endothelial cells during the angiogenic process. Nonetheless, the persistence of human vasculature suggests the SCID-human model can be used to study the interaction between bone-seeking tumor cells, such as prostate cancer, and human bone endothelium in vivo, and to test potential therapeutic strategies which may depend on the presence of human vessels.

angiogenesis bone metastasis endothelium mouse model prostate cancer 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Abrams HL, Spiro R, Goldstein N. Metastases in carcinoma: analysis of 1000 autopsied cases. Cancer 1950; 3: 74–85.PubMedCrossRefGoogle Scholar
  2. 2.
    Wu TT, Sikes RA, Cui Q et al. Establishing human prostate cancer cell xenografts in bone: induction of osteoblastic reaction by prostatespecific antigen-producing tumors in athymic and SCID/bg mice using LNCaP and lineage-derived metastatic sublines. Int J Cancer 1998; 77(6): 887–94.PubMedCrossRefGoogle Scholar
  3. 3.
    Thalmann GN, Anezinis PE, Chang SM et al. Androgen-independent cancer progression and bone metastasis in the LNCaP model of human prostate cancer [published erratum appeared in Cancer Res 1994 Jul 15; 54(14): 3953]. Cancer Res 1994; 54(10): 2577–81.PubMedGoogle Scholar
  4. 4.
    Wang M, Stearns ME. Isolation and characterization of PC-3 human prostatic tumor sublines which preferentially metastasize to select organs in S.C.I.D. mice. Differentiation 1991; 48(2): 115–25.PubMedGoogle Scholar
  5. 5.
    Nemeth JA, Harb JF, Barroso U, Jr et al. Severe combined immunodeficient-hu model of human prostate cancer metastasis to human bone. Cancer Res 1999; 59(8): 1987–93.Google Scholar
  6. 6.
    Urashima M, Chen BP, Chen S et al. The development of a model for the homing of multiple myeloma cells to human bone marrow. Blood 1997; 90(2): 754–65.PubMedGoogle Scholar
  7. 7.
    Teraoka S, Kyoizumi S, Seyama T et al. A novel SCID mouse model for studying spontaneous metastasis of human lung cancer to human tissue. Jpn J Cancer Res 1995; 86(5): 419–23.PubMedGoogle Scholar
  8. 8.
    Shtivelman E, Namikawa R. Species-specific metastasis of human tumor cells in the severe combined immunodeficiency mouse engrafted with human tissue. Proc Natl Acad Sci USA 1995; 92(10): 4661–5.PubMedCrossRefGoogle Scholar
  9. 9.
    Sampson-Johannes A, Wang W, Shtivelman E. Colonization of human lung grafts in SCID-hu mice by human colon carcinoma cells. Int J Cancer 1996; 65(6): 864–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Demarchez M, Hartmann DJ, Prunieras M. An immunohistological study of the revascularization process in human skin transplanted onto the nude mouse. Transplantation 1987; 43(6): 896–903.PubMedCrossRefGoogle Scholar
  11. 11.
    Kaufmann R, Mielke V, Reimann J et al. Cellular and molecular composition of human skin in long-term xenografts on SCID mice. Exp Dermatol 1993; 2(5): 209–16.PubMedCrossRefGoogle Scholar
  12. 12.
    Yan HC, Juhasz I, Pilewski J et al. Human/severe combined immunodeficient mouse chimeras. An experimental in vivo model system to study the regulation of human endothelial cell-leukocyte adhesion molecules. J Clin Invest 1993; 91(3): 986–96.PubMedCrossRefGoogle Scholar
  13. 13.
    Pilewski JM, Panettieri RA, Jr., Kaiser LR et al. Expression of endothelial cell adhesion molecules in human bronchial xenografts. Am J Respir Crit Care Med 1994; 150(3): 795–801.PubMedGoogle Scholar
  14. 14.
    Parums DV, Cordell JL, Micklem K et al. JC70: a new monoclonal antibody that detects vascular endothelium associated antigen on routinely processed tissue sections. J Clin Pathol 1990; 43(9): 752–7.PubMedGoogle Scholar
  15. 15.
    Wilson MJ, Sinha AA. Human prostate tumor angiogenesis in nude mice: metalloprotease and plasminogen activator activities during tumor growth and neovascularization of subcutaneously injected matrigel impregnated with human prostate tumor cells. Anat Rec 1997; 249(1): 63–73.PubMedCrossRefGoogle Scholar
  16. 16.
    Eberhard A, Kahlert S, Goede V et al. Heterogeneity of angiogenesis and blood vessel maturation in human tumors: implications for antiangiogenic tumor therapies. Cancer Res 2000; 60(5): 1388–93.PubMedGoogle Scholar
  17. 17.
    Juhasz I, Albelda SM, Elder DE et al. Growth and invasion of human melanomas in human skin grafted to immunodeficient mice. Am J Pathol 1993; 143(2): 528–37.PubMedGoogle Scholar
  18. 18.
    Romanov VI, Goligorsky MS. RGD-recognizing integrins mediate interactions of human prostate carcinoma cells with endothelial cells in vitro. Prostate 1999; 39(2): 108–18.PubMedCrossRefGoogle Scholar
  19. 19.
    Lehr JE, Pienta KJ. Preferential adhesion of prostate cancer cells to a human bone marrow endothelial cell line [see comments]. J Natl Cancer Inst 1998; 90(2): 118–23.CrossRefGoogle Scholar
  20. 20.
    Pasqualini R, Ruoslahti E. Organ targeting in vivo using phage display peptide libraries. Nature 1996; 380(6572): 364–6.PubMedCrossRefGoogle Scholar
  21. 21.
    Magro C, Orr FW, Manishen WJ et al. Adhesion, chemotaxis, and aggregation of Walker carcinosarcoma cells in response to products of resorbing bone. J Natl Cancer Inst 1985; 74(4): 829–38.PubMedGoogle Scholar
  22. 22.
    Kostenuik PJ, Sanchez-Sweatman O, Orr FW et al. Bone cell matrix promotes the adhesion of human prostatic carcinoma cells via the alpha 2 beta 1 integrin. Clin Exp Metastasis 1996; 14(1): 19–26.PubMedCrossRefGoogle Scholar
  23. 23.
    Potter KM, Juacaba SF, Price JE et al. Observations on organ distribution of fluorescein-labelled tumour cells released intravascularly. Invasion Metastasis 1983; 3(4): 221–33.PubMedGoogle Scholar
  24. 24.
    Yang M, Jiang P, Sun FX et al. A fluorescent orthotopic bone metastasis model of human prostate cancer. Cancer Res 1999; 59(4): 781–6.Google Scholar
  25. 25.
    Heike Y, Ohira T, Takahashi M et al. Long-term human hematopoiesis in SCID-hu mice bearing transplanted fragments of adult bone and bone marrow cells. Blood 1995; 86(2): 524–30.PubMedGoogle Scholar
  26. 26.
    Kyoizumi S, Baum CM, Kaneshima H et al. Implantation and maintenance of functional human bone marrow in SCID-hu mice. Blood 1992; 79(7): 1704–11.PubMedGoogle Scholar
  27. 27.
    Arap W, Pasqualini R, Ruoslahti E. Cancer treatment by targeted drug delivery to tumor vasculature in a mouse model [see comments]. Science 1998; 279(5349): 377–80.PubMedCrossRefGoogle Scholar
  28. 28.
    Pasqualini R, Koivunen E, Kain R et al. Aminopeptidase N is a receptor for tumor-homing peptides and a target for inhibiting angiogenesis. Cancer Res 2000; 60(3): 722–7.PubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 2000

Authors and Affiliations

  • Jeffrey A. Nemeth
    • 1
  • Jason W. Roberts
    • 1
  • Chadwick M. Mullins
    • 1
  • Michael L. Cher
    • 1
  1. 1.Departments of Urology and 2PathologyWayne State University School of Medicine and The Barbara Ann Karmanos Cancer InstituteDetroitUSA

Personalised recommendations