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. 1994 Jul;145(1):74–79.

Oncostatin-M is an autocrine growth factor in Kaposi's sarcoma.

J Cai 1, P S Gill 1, R Masood 1, P Chandrasoma 1, B Jung 1, R E Law 1, S F Radka 1
PMCID: PMC1887313  PMID: 8030759

Abstract

Oncostatin-M is a cytokine produced by macrophages and activated T lymphocytes that has recently been shown to be a mitogen for AIDS-related Kaposi's sarcoma (KS)-derived spindle cells. The significance of oncostatin-M production in AIDS-related KS in vivo, however, remains unknown. In this study we wanted to determine whether oncostatin-M is expressed in vivo in patients with HIV-I-related KS, define the cell types that express this cytokine, and compared with the control tissues from HIV-I-negative individuals. A second objective of our study was to define the expression of oncostatin-M in AIDS-KS-derived spindle cell isolates cultured in vitro and to determine whether oncostatin-M is an autocrine growth factor for these KS cells. We have determined that oncostatin-M is not expressed in any of the several organs examined in control cases, whereas the tumor tissue obtained from the skin biopsies of HIV-I-infected cases with KS displayed oncostatin-M expression in the spindle cell components of the tumor, as well as the cells lining the vascular structures, smooth muscle cells lining the eccrine sweat glands, and the epidermal layers of the skin. Furthermore, uninvolved skin of patients with HIV-related KS express oncostatin-M in the cells lining normal vessels. The mRNA polymerase chain reaction analysis confirmed findings in the primary tissues and showed expression in all of the AIDS-KS-derived spindle cell isolates examined. We have also shown with the use of oncostatin-M-specific antisense oligodeoxynucleotides that KS cell proliferation is inhibited, which correlated with a more precipitous decline in the production of interleukin-6 by these cells. We conclude that oncostatin-M is only expressed in the skin and KS tumor of HIV-I-infected individuals. Furthermore, we provide evidence that oncostatin-M is an autocrine growth factor for KS.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Brown T. J., Rowe J. M., Liu J. W., Shoyab M. Regulation of IL-6 expression by oncostatin M. J Immunol. 1991 Oct 1;147(7):2175–2180. [PubMed] [Google Scholar]
  2. 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]
  3. Hamilton A. S., Radka S. F., Bernstein L., Gill P. S., Gonsalves M., Naemura J. R., Ross R. K. Relationship of serum levels of oncostatin M to AIDS-related and classic Kaposi's sarcoma. J Acquir Immune Defic Syndr. 1994 Apr;7(4):410–414. [PubMed] [Google Scholar]
  4. Masood R., Husain S. R., Rahman A., Gill P. Potentiation of cytotoxicity of Kaposi's sarcoma related to immunodeficiency syndrome (AIDS) by liposome-encapsulated doxorubicin. AIDS Res Hum Retroviruses. 1993 Aug;9(8):741–746. doi: 10.1089/aid.1993.9.741. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. Miles S. A., Rezai A. R., Salazar-González J. F., Vander Meyden M., Stevens R. H., Logan D. M., Mitsuyasu R. T., Taga T., Hirano T., Kishimoto T. AIDS Kaposi sarcoma-derived cells produce and respond to interleukin 6. Proc Natl Acad Sci U S A. 1990 Jun;87(11):4068–4072. doi: 10.1073/pnas.87.11.4068. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Nakamura S., Salahuddin S. Z., Biberfeld P., Ensoli B., Markham P. D., Wong-Staal F., Gallo R. C. Kaposi's sarcoma cells: long-term culture with growth factor from retrovirus-infected CD4+ T cells. Science. 1988 Oct 21;242(4877):426–430. doi: 10.1126/science.3262925. [DOI] [PubMed] [Google Scholar]
  9. Radka S. F., Naemura J. R., Shoyab M. Abrogation of the antiproliferative activity of oncostatin M by a monoclonal antibody. Cytokine. 1992 May;4(3):221–226. doi: 10.1016/1043-4666(92)90059-z. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Zarling J. M., Shoyab M., Marquardt H., Hanson M. B., Lioubin M. N., Todaro G. J. Oncostatin M: a growth regulator produced by differentiated histiocytic lymphoma cells. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9739–9743. doi: 10.1073/pnas.83.24.9739. [DOI] [PMC free article] [PubMed] [Google Scholar]

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