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The American Journal of Pathology logoLink to The American Journal of Pathology
. 1994 Jan;144(1):51–59.

Vascular origin of Kaposi's sarcoma. Expression of leukocyte adhesion molecule-1, thrombomodulin, and tissue factor.

Y M Zhang 1, S Bachmann 1, C Hemmer 1, J van Lunzen 1, A von Stemm 1, P Kern 1, M Dietrich 1, R Ziegler 1, R Waldherr 1, P P Nawroth 1
PMCID: PMC1887124  PMID: 7507301

Abstract

We studied seven cases of Kaposi's sarcomas (KS) obtained from patients with AIDS and one KS from a patient without HIV infection. Antigen expression was studied by immunocytochemistry and mRNA expression by in situ hybridisation. The markers tested were endothelial leukocyte adhesion molecule-1, thrombomodulin, and tissue factor. In all tumors (AIDS and non-AIDS associated) these markers reacted positive, indicating transcription and translation of these genes in KS. The synthesis and expression of tissue factor and thrombomodulin suggests that KS is a tumor that has tissue factor-mediated thrombin formation under the control of thrombomodulin. The expression of thrombomodulin and endothelial leukocyte adhesion molecule-1 provides evidence for the vascular origin of KS.

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Selected References

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  1. Ackerman A. B. Subtle clues to diagnosis by conventional microscopy. The patch stage of Kaposi's sarcoma. Am J Dermatopathol. 1979 Summer;1(2):165–172. doi: 10.1097/00000372-197900120-00011. [DOI] [PubMed] [Google Scholar]
  2. Barillari G., Buonaguro L., Fiorelli V., Hoffman J., Michaels F., Gallo R. C., Ensoli B. Effects of cytokines from activated immune cells on vascular cell growth and HIV-1 gene expression. Implications for AIDS-Kaposi's sarcoma pathogenesis. J Immunol. 1992 Dec 1;149(11):3727–3734. [PubMed] [Google Scholar]
  3. Bevilacqua M. P., Gimbrone M. A., Jr Inducible endothelial functions in inflammation and coagulation. Semin Thromb Hemost. 1987 Oct;13(4):425–433. doi: 10.1055/s-2007-1003519. [DOI] [PubMed] [Google Scholar]
  4. Bevilacqua M. P., Pober J. S., Mendrick D. L., Cotran R. S., Gimbrone M. A., Jr Identification of an inducible endothelial-leukocyte adhesion molecule. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9238–9242. doi: 10.1073/pnas.84.24.9238. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bevilacqua M. P., Pober J. S., Wheeler M. E., Cotran R. S., Gimbrone M. A., Jr Interleukin 1 acts on cultured human vascular endothelium to increase the adhesion of polymorphonuclear leukocytes, monocytes, and related leukocyte cell lines. J Clin Invest. 1985 Nov;76(5):2003–2011. doi: 10.1172/JCI112200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bevilacqua M. P., Stengelin S., Gimbrone M. A., Jr, Seed B. Endothelial leukocyte adhesion molecule 1: an inducible receptor for neutrophils related to complement regulatory proteins and lectins. Science. 1989 Mar 3;243(4895):1160–1165. doi: 10.1126/science.2466335. [DOI] [PubMed] [Google Scholar]
  7. Dittman W. A., Majerus P. W. Structure and function of thrombomodulin: a natural anticoagulant. Blood. 1990 Jan 15;75(2):329–336. [PubMed] [Google Scholar]
  8. Ensoli B., Barillari G., Salahuddin S. Z., Gallo R. C., Wong-Staal F. Tat protein of HIV-1 stimulates growth of cells derived from Kaposi's sarcoma lesions of AIDS patients. Nature. 1990 May 3;345(6270):84–86. doi: 10.1038/345084a0. [DOI] [PubMed] [Google Scholar]
  9. Ensoli B., Nakamura S., Salahuddin S. Z., Biberfeld P., Larsson L., Beaver B., Wong-Staal F., Gallo R. C. AIDS-Kaposi's sarcoma-derived cells express cytokines with autocrine and paracrine growth effects. Science. 1989 Jan 13;243(4888):223–226. doi: 10.1126/science.2643161. [DOI] [PubMed] [Google Scholar]
  10. Ensoli B., Salahuddin S. Z., Gallo R. C. AIDS-associated Kaposi's sarcoma: a molecular model for its pathogenesis. Cancer Cells. 1989 Nov;1(3):93–96. [PubMed] [Google Scholar]
  11. Esmon C. T. The regulation of natural anticoagulant pathways. Science. 1987 Mar 13;235(4794):1348–1352. doi: 10.1126/science.3029867. [DOI] [PubMed] [Google Scholar]
  12. Goerdt S., Sorg C. Endothelial heterogeneity and the acquired immunodeficiency syndrome: a paradigm for the pathogenesis of vascular disorders. Clin Investig. 1992 Feb;70(2):89–98. doi: 10.1007/BF00227347. [DOI] [PubMed] [Google Scholar]
  13. Gottlieb G. J., Ackerman A. B. Kaposi's sarcoma: an extensively disseminated form in young homosexual men. Hum Pathol. 1982 Oct;13(10):882–892. doi: 10.1016/s0046-8177(82)80047-6. [DOI] [PubMed] [Google Scholar]
  14. Imada S., Yamaguchi H., Nagumo M., Katayanagi S., Iwasaki H., Imada M. Identification of fetomodulin, a surface marker protein of fetal development, as thrombomodulin by gene cloning and functional assays. Dev Biol. 1990 Jul;140(1):113–122. doi: 10.1016/0012-1606(90)90058-q. [DOI] [PubMed] [Google Scholar]
  15. Ishii H., Uchiyama H., Kazama M. Soluble thrombomodulin antigen in conditioned medium is increased by damage of endothelial cells. Thromb Haemost. 1991 May 6;65(5):618–623. [PubMed] [Google Scholar]
  16. Lathey J. L., Agosti J. M., Nelson J. A., Corey L., Gregory S. A., Morrissey J. H., Edgington T. S., Oldstone M. B. A selective defect in tissue factor mRNA expression in monocytes from AIDS patients. Clin Immunol Immunopathol. 1990 Jan;54(1):1–13. doi: 10.1016/0090-1229(90)90001-7. [DOI] [PubMed] [Google Scholar]
  17. Maruyama I., Bell C. E., Majerus P. W. Thrombomodulin is found on endothelium of arteries, veins, capillaries, and lymphatics, and on syncytiotrophoblast of human placenta. J Cell Biol. 1985 Aug;101(2):363–371. doi: 10.1083/jcb.101.2.363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Miles S. A., Martínez-Maza O., Rezai A., Magpantay L., Kishimoto T., Nakamura S., Radka S. F., Linsley P. S. Oncostatin M as a potent mitogen for AIDS-Kaposi's sarcoma-derived cells. Science. 1992 Mar 13;255(5050):1432–1434. doi: 10.1126/science.1542793. [DOI] [PubMed] [Google Scholar]
  19. Nair B. C., DeVico A. L., Nakamura S., Copeland T. D., Chen Y., Patel A., O'Neil T., Oroszlan S., Gallo R. C., Sarngadharan M. G. Identification of a major growth factor for AIDS-Kaposi's sarcoma cells as oncostatin M. Science. 1992 Mar 13;255(5050):1430–1432. doi: 10.1126/science.1542792. [DOI] [PubMed] [Google Scholar]
  20. Nawroth P. P., Handley D. A., Esmon C. T., Stern D. M. Interleukin 1 induces endothelial cell procoagulant while suppressing cell-surface anticoagulant activity. Proc Natl Acad Sci U S A. 1986 May;83(10):3460–3464. doi: 10.1073/pnas.83.10.3460. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Nawroth P. P., Stern D. M. Endothelial cell procoagulant properties and the host response. Semin Thromb Hemost. 1987 Oct;13(4):391–397. doi: 10.1055/s-2007-1003516. [DOI] [PubMed] [Google Scholar]
  22. Nawroth P. P., Stern D. M. Modulation of endothelial cell hemostatic properties by tumor necrosis factor. J Exp Med. 1986 Mar 1;163(3):740–745. doi: 10.1084/jem.163.3.740. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. O'Connell K., Landman G., Farmer E., Edidin M. Endothelial cells transformed by SV40 T antigen cause Kaposi's sarcomalike tumors in nude mice. Am J Pathol. 1991 Oct;139(4):743–749. [PMC free article] [PubMed] [Google Scholar]
  24. Picker L. J., Kishimoto T. K., Smith C. W., Warnock R. A., Butcher E. C. ELAM-1 is an adhesion molecule for skin-homing T cells. Nature. 1991 Feb 28;349(6312):796–799. doi: 10.1038/349796a0. [DOI] [PubMed] [Google Scholar]
  25. Pober J. S., Cotran R. S. The role of endothelial cells in inflammation. Transplantation. 1990 Oct;50(4):537–544. doi: 10.1097/00007890-199010000-00001. [DOI] [PubMed] [Google Scholar]
  26. Pober J. S. Warner-Lambert/Parke-Davis award lecture. Cytokine-mediated activation of vascular endothelium. Physiology and pathology. Am J Pathol. 1988 Dec;133(3):426–433. [PMC free article] [PubMed] [Google Scholar]
  27. Roth W. K., Werner S., Risau W., Remberger K., Hofschneider P. H. Cultured, AIDS-related Kaposi's sarcoma cells express endothelial cell markers and are weakly malignant in vitro. Int J Cancer. 1988 Nov 15;42(5):767–773. doi: 10.1002/ijc.2910420523. [DOI] [PubMed] [Google Scholar]
  28. Rutgers J. L., Wieczorek R., Bonetti F., Kaplan K. L., Posnett D. N., Friedman-Kien A. E., Knowles D. M., 2nd The expression of endothelial cell surface antigens by AIDS-associated Kaposi's sarcoma. Evidence for a vascular endothelial cell origin. Am J Pathol. 1986 Mar;122(3):493–499. [PMC free article] [PubMed] [Google Scholar]
  29. Salahuddin S. Z., Nakamura S., Biberfeld P., Kaplan M. H., Markham P. D., Larsson L., Gallo R. C. Angiogenic properties of Kaposi's sarcoma-derived cells after long-term culture in vitro. Science. 1988 Oct 21;242(4877):430–433. doi: 10.1126/science.2459779. [DOI] [PubMed] [Google Scholar]
  30. Sankey E. A., More L., Dhillon A. P. QBEnd/10: a new immunostain for the routine diagnosis of Kaposi's sarcoma. J Pathol. 1990 Jul;161(3):267–271. doi: 10.1002/path.1711610315. [DOI] [PubMed] [Google Scholar]
  31. Scarpati E. M., Wen D., Broze G. J., Jr, Miletich J. P., Flandermeyer R. R., Siegel N. R., Sadler J. E. Human tissue factor: cDNA sequence and chromosome localization of the gene. Biochemistry. 1987 Aug 25;26(17):5234–5238. doi: 10.1021/bi00391a004. [DOI] [PubMed] [Google Scholar]
  32. Scully P. A., Steinman H. K., Kennedy C., Trueblood K., Frisman D. M., Voland J. R. AIDS-related Kaposi's sarcoma displays differential expression of endothelial surface antigens. Am J Pathol. 1988 Feb;130(2):244–251. [PMC free article] [PubMed] [Google Scholar]
  33. Shimizu Y., Shaw S., Graber N., Gopal T. V., Horgan K. J., Van Seventer G. A., Newman W. Activation-independent binding of human memory T cells to adhesion molecule ELAM-1. Nature. 1991 Feb 28;349(6312):799–802. doi: 10.1038/349799a0. [DOI] [PubMed] [Google Scholar]
  34. Soff G. A., Jackman R. W., Rosenberg R. D. Expression of thrombomodulin by smooth muscle cells in culture: different effects of tumor necrosis factor and cyclic adenosine monophosphate on thrombomodulin expression by endothelial cells and smooth muscle cells in culture. Blood. 1991 Feb 1;77(3):515–518. [PubMed] [Google Scholar]
  35. Stoica G., Hoffman J., Yuen P. H. Moloney murine sarcoma virus 349 induces Kaposi's sarcomalike lesions in Balb/c mice. Am J Pathol. 1990 Apr;136(4):933–947. [PMC free article] [PubMed] [Google Scholar]
  36. Vogel J., Hinrichs S. H., Reynolds R. K., Luciw P. A., Jay G. The HIV tat gene induces dermal lesions resembling Kaposi's sarcoma in transgenic mice. Nature. 1988 Oct 13;335(6191):606–611. doi: 10.1038/335606a0. [DOI] [PubMed] [Google Scholar]
  37. Weich H. A., Salahuddin S. Z., Gill P., Nakamura S., Gallo R. C., Folkmann J. AIDS-associated Kaposi's sarcoma-derived cells in long-term culture express and synthesize smooth muscle alpha-actin. Am J Pathol. 1991 Dec;139(6):1251–1258. [PMC free article] [PubMed] [Google Scholar]
  38. Wen D. Z., Dittman W. A., Ye R. D., Deaven L. L., Majerus P. W., Sadler J. E. Human thrombomodulin: complete cDNA sequence and chromosome localization of the gene. Biochemistry. 1987 Jul 14;26(14):4350–4357. doi: 10.1021/bi00388a025. [DOI] [PubMed] [Google Scholar]

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