Skip to main content
NCBI home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1991 Dec;139(6):1251–1258.

AIDS-associated Kaposi's sarcoma-derived cells in long-term culture express and synthesize smooth muscle alpha-actin.

H A Weich 1, S Z Salahuddin 1, P Gill 1, S Nakamura 1, R C Gallo 1, J Folkmann 1
PMCID: PMC1886449  PMID: 1750501

Abstract

Spindle-shaped cells from Kaposi's sarcoma lesions (AIDS-KS cells) were cultured for long periods in the presence of conditioned medium from activated CD4-positive T cells (HTLV-II infected transformed nonvirus producer) and characterized under in vitro conditions. To investigate a possible vascular origin, AIDS-KS cells were analyzed for the presence of smooth muscle alpha-actin, a differentiation marker for vascular smooth muscle cells. Immunofluorescence studies using a monoclonal antibody for smooth muscle alpha-actin demonstrated positive staining of the AIDS-KS cells (KS-3 and KS-4) but not by endothelial cells or fibroblasts. Northern blot analysis using an oligonucleotide probe unique for human smooth muscle alpha-actin indicated the expression of this gene by AIDS-KS cells. Similar analysis of biopsies from the KS lesion showed that in addition to the staining of smooth muscle cells associated with the blood vessels, the tumor-related spindle cells also stained positively. These cells were also analyzed for the expression of different growth factor genes. The platelet-derived growth factor (PDGF) A-chain gene was expressed at a moderate level. The insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-2 (IGF-2) genes were not overexpressed in relation to control cells. These data suggest that the analyzed AIDS-KS cells may be smooth muscle-like cells and therefore of vascular origin. Based on these results as well as previous reports, we speculate that cells of the immune system may regulate growth of cells in the vascular wall by a novel pathway.

Full text

PDF
1251

Images in this article

1254Figure 1
on p.1254
1255Figure 3
on p.1255
1255Figure 2
on p.1255
1256Figure 4
on p.1256

Selected References

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

  1. Barrett T. B., Benditt E. P. Platelet-derived growth factor gene expression in human atherosclerotic plaques and normal artery wall. Proc Natl Acad Sci U S A. 1988 Apr;85(8):2810–2814. doi: 10.1073/pnas.85.8.2810. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barrett T. B., Gajdusek C. M., Schwartz S. M., McDougall J. K., Benditt E. P. Expression of the sis gene by endothelial cells in culture and in vivo. Proc Natl Acad Sci U S A. 1984 Nov;81(21):6772–6774. doi: 10.1073/pnas.81.21.6772. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  4. Collins T., Pober J. S., Gimbrone M. A., Jr, Hammacher A., Betsholtz C., Westermark B., Heldin C. H. Cultured human endothelial cells express platelet-derived growth factor A chain. Am J Pathol. 1987 Jan;126(1):7–12. [PMC free article] [PubMed] [Google Scholar]
  5. Darby I., Skalli O., Gabbiani G. Alpha-smooth muscle actin is transiently expressed by myofibroblasts during experimental wound healing. Lab Invest. 1990 Jul;63(1):21–29. [PubMed] [Google Scholar]
  6. Delli Bovi P., Curatola A. M., Kern F. G., Greco A., Ittmann M., Basilico C. An oncogene isolated by transfection of Kaposi's sarcoma DNA encodes a growth factor that is a member of the FGF family. Cell. 1987 Aug 28;50(5):729–737. doi: 10.1016/0092-8674(87)90331-x. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Hoppe J., Schumacher L., Eichner W., Weich H. A. The long 3'-untranslated regions of the PDGF-A and -B mRNAs are only distantly related. FEBS Lett. 1987 Nov 2;223(2):243–246. doi: 10.1016/0014-5793(87)80297-1. [DOI] [PubMed] [Google Scholar]
  9. Höppener J. W., Mosselman S., Roholl P. J., Lambrechts C., Slebos R. J., de Pagter-Holthuizen P., Lips C. J., Jansz H. S., Sussenbach J. S. Expression of insulin-like growth factor-I and -II genes in human smooth muscle tumours. EMBO J. 1988 May;7(5):1379–1385. doi: 10.1002/j.1460-2075.1988.tb02954.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Irminger J. C., Rosen K. M., Humbel R. E., Villa-Komaroff L. Tissue-specific expression of insulin-like growth factor II mRNAs with distinct 5' untranslated regions. Proc Natl Acad Sci U S A. 1987 Sep;84(18):6330–6334. doi: 10.1073/pnas.84.18.6330. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Jansen M., van Schaik F. M., Ricker A. T., Bullock B., Woods D. E., Gabbay K. H., Nussbaum A. L., Sussenbach J. S., Van den Brande J. L. Sequence of cDNA encoding human insulin-like growth factor I precursor. Nature. 1983 Dec 8;306(5943):609–611. doi: 10.1038/306609a0. [DOI] [PubMed] [Google Scholar]
  12. Johnson R. J., Iida H., Alpers C. E., Majesky M. W., Schwartz S. M., Pritzi P., Gordon K., Gown A. M. Expression of smooth muscle cell phenotype by rat mesangial cells in immune complex nephritis. Alpha-smooth muscle actin is a marker of mesangial cell proliferation. J Clin Invest. 1991 Mar;87(3):847–858. doi: 10.1172/JCI115089. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Jonasson L., Holm J., Hansson G. K. Cyclosporin A inhibits smooth muscle proliferation in the vascular response to injury. Proc Natl Acad Sci U S A. 1988 Apr;85(7):2303–2306. doi: 10.1073/pnas.85.7.2303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kocher O., Madri J. A. Modulation of actin mRNAs in cultured vascular cells by matrix components and TGF-beta 1. In Vitro Cell Dev Biol. 1989 May;25(5):424–434. doi: 10.1007/BF02624627. [DOI] [PubMed] [Google Scholar]
  15. Liesveld J. L., Abboud C. N., Duerst R. E., Ryan D. H., Brennan J. K., Lichtman M. A. Characterization of human marrow stromal cells: role in progenitor cell binding and granulopoiesis. Blood. 1989 May 15;73(7):1794–1800. [PubMed] [Google Scholar]
  16. Majesky M. W., Benditt E. P., Schwartz S. M. Expression and developmental control of platelet-derived growth factor A-chain and B-chain/Sis genes in rat aortic smooth muscle cells. Proc Natl Acad Sci U S A. 1988 Mar;85(5):1524–1528. doi: 10.1073/pnas.85.5.1524. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. Netland P. A., Zetter B. R., Via D. P., Voyta J. C. In situ labelling of vascular endothelium with fluorescent acetylated low density lipoprotein. Histochem J. 1985 Dec;17(12):1309–1320. doi: 10.1007/BF01002528. [DOI] [PubMed] [Google Scholar]
  19. Reynolds W. A., Winkelmann R. K., Soule E. H. Kaposi's sarcoma: a clinicopathologic study with particular reference to its relationship to the reticuloendothelial system. Medicine (Baltimore) 1965 Sep;44(5):419–443. doi: 10.1097/00005792-196509000-00003. [DOI] [PubMed] [Google Scholar]
  20. Sakamoto H., Mori M., Taira M., Yoshida T., Matsukawa S., Shimizu K., Sekiguchi M., Terada M., Sugimura T. Transforming gene from human stomach cancers and a noncancerous portion of stomach mucosa. Proc Natl Acad Sci U S A. 1986 Jun;83(11):3997–4001. doi: 10.1073/pnas.83.11.3997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. 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]
  22. Schmitt-Gräff A., Krüger S., Bochard F., Gabbiani G., Denk H. Modulation of alpha smooth muscle actin and desmin expression in perisinusoidal cells of normal and diseased human livers. Am J Pathol. 1991 May;138(5):1233–1242. [PMC free article] [PubMed] [Google Scholar]
  23. Sejersen T., Betsholtz C., Sjölund M., Heldin C. H., Westermark B., Thyberg J. Rat skeletal myoblasts and arterial smooth muscle cells express the gene for the A chain but not the gene for the B chain (c-sis) of platelet-derived growth factor (PDGF) and produce a PDGF-like protein. Proc Natl Acad Sci U S A. 1986 Sep;83(18):6844–6848. doi: 10.1073/pnas.83.18.6844. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Skalli O., Ropraz P., Trzeciak A., Benzonana G., Gillessen D., Gabbiani G. A monoclonal antibody against alpha-smooth muscle actin: a new probe for smooth muscle differentiation. J Cell Biol. 1986 Dec;103(6 Pt 2):2787–2796. doi: 10.1083/jcb.103.6.2787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Skalli O., Schürch W., Seemayer T., Lagacé R., Montandon D., Pittet B., Gabbiani G. Myofibroblasts from diverse pathologic settings are heterogeneous in their content of actin isoforms and intermediate filament proteins. Lab Invest. 1989 Feb;60(2):275–285. [PubMed] [Google Scholar]
  26. Taira M., Yoshida T., Miyagawa K., Sakamoto H., Terada M., Sugimura T. cDNA sequence of human transforming gene hst and identification of the coding sequence required for transforming activity. Proc Natl Acad Sci U S A. 1987 May;84(9):2980–2984. doi: 10.1073/pnas.84.9.2980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Ueyama H., Hamada H., Battula N., Kakunaga T. Structure of a human smooth muscle actin gene (aortic type) with a unique intron site. Mol Cell Biol. 1984 Jun;4(6):1073–1078. doi: 10.1128/mcb.4.6.1073. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Weich H. A., Herbst D., Schairer H. U., Hoppe J. Platelet-derived growth factor. Phorbol ester induces the expression of the B-chain but not of the A-chain in HEL cells. FEBS Lett. 1987 Mar 9;213(1):89–94. doi: 10.1016/0014-5793(87)81470-9. [DOI] [PubMed] [Google Scholar]
  29. Weich H. A., Iberg N., Klagsbrun M., Folkman J. Expression of acidic and basic fibroblast growth factors in human and bovine vascular smooth muscle cells. Growth Factors. 1990;2(4):313–320. doi: 10.3109/08977199009167026. [DOI] [PubMed] [Google Scholar]
  30. Weich H. A., Sebald W., Schairer H. U., Hoppe J. The human osteosarcoma cell line U-2 OS expresses a 3.8 kilobase mRNA which codes for the sequence of the PDGF-B chain. FEBS Lett. 1986 Mar 31;198(2):344–348. doi: 10.1016/0014-5793(86)80433-1. [DOI] [PubMed] [Google Scholar]
  31. Yoshida T., Tsutsumi M., Sakamoto H., Miyagawa K., Teshima S., Sugimura T., Terada M. Expression of the HST1 oncogene in human germ cell tumors. Biochem Biophys Res Commun. 1988 Sep 30;155(3):1324–1329. doi: 10.1016/s0006-291x(88)81286-5. [DOI] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES