Skip to main content
PMC home page
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1991 Jun;11(6):3125–3131. doi: 10.1128/mcb.11.6.3125

Suppression of tumor formation in vivo by expression of the JE gene in malignant cells.

B J Rollins 1, M E Sunday 1
PMCID: PMC360158  PMID: 2038321

Abstract

The early growth response gene JE encodes a monocyte chemoattractant, MCP-1. The JE/MCP-1 protein attracts and stimulates human monocytes and induces monocyte-mediated inhibition of tumor cell growth in vitro. Expression of human or murine JE/MCP-1 in Chinese hamster ovary (CHO) cells completely suppressed their ability to form tumors in nude mice. Coinjection of JE/MCP-1-expressing cells with nonexpressing CHO cells or with HeLa cells also prevented tumor formation. Since JE/MCP-1 expression had no discernible effect on the tranformed phenotype of these cells in vitro, the suppressive effect depends on host animal factors. These factors are likely to be components of the inflammatory response, because JE/MCP-1-expressing cells elicited a predominantly monocytic infiltrate at the site of injection. Our results suggest that JE/MCP-1 protein may be useful in cancer therapy.

Full text

PDF
3125

Images in this article

3126Image
on p.3126
3128Image
on p.3128
3129Image
on p.3129

Selected References

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

  1. Chaney W. G., Howard D. R., Pollard J. W., Sallustio S., Stanley P. High-frequency transfection of CHO cells using polybrene. Somat Cell Mol Genet. 1986 May;12(3):237–244. doi: 10.1007/BF01570782. [DOI] [PubMed] [Google Scholar]
  2. Cianciolo G. J., Snyderman R. Effects of tumor growth on host defenses. Cancer Metastasis Rev. 1986;5(1):15–27. doi: 10.1007/BF00049528. [DOI] [PubMed] [Google Scholar]
  3. Cochran B. H., Reffel A. C., Stiles C. D. Molecular cloning of gene sequences regulated by platelet-derived growth factor. Cell. 1983 Jul;33(3):939–947. doi: 10.1016/0092-8674(83)90037-5. [DOI] [PubMed] [Google Scholar]
  4. Donlon T. A., Krensky A. M., Wallace M. R., Collins F. S., Lovett M., Clayberger C. Localization of a human T-cell-specific gene, RANTES (D17S136E), to chromosome 17q11.2-q12. Genomics. 1990 Mar;6(3):548–553. doi: 10.1016/0888-7543(90)90485-d. [DOI] [PubMed] [Google Scholar]
  5. Falk W., Goodwin R. H., Jr, Leonard E. J. A 48-well micro chemotaxis assembly for rapid and accurate measurement of leukocyte migration. J Immunol Methods. 1980;33(3):239–247. doi: 10.1016/0022-1759(80)90211-2. [DOI] [PubMed] [Google Scholar]
  6. Furutani Y., Nomura H., Notake M., Oyamada Y., Fukui T., Yamada M., Larsen C. G., Oppenheim J. J., Matsushima K. Cloning and sequencing of the cDNA for human monocyte chemotactic and activating factor (MCAF). Biochem Biophys Res Commun. 1989 Feb 28;159(1):249–255. doi: 10.1016/0006-291x(89)92430-3. [DOI] [PubMed] [Google Scholar]
  7. Graves D. T., Jiang Y. L., Williamson M. J., Valente A. J. Identification of monocyte chemotactic activity produced by malignant cells. Science. 1989 Sep 29;245(4925):1490–1493. doi: 10.1126/science.2781291. [DOI] [PubMed] [Google Scholar]
  8. Griffin C. A., Emanuel B. S., LaRocco P., Schwartz E., Poncz M. Human platelet factor 4 gene is mapped to 4q12----q21. Cytogenet Cell Genet. 1987;45(2):67–69. doi: 10.1159/000132431. [DOI] [PubMed] [Google Scholar]
  9. Irving S. G., Zipfel P. F., Balke J., McBride O. W., Morton C. C., Burd P. R., Siebenlist U., Kelly K. Two inflammatory mediator cytokine genes are closely linked and variably amplified on chromosome 17q. Nucleic Acids Res. 1990 Jun 11;18(11):3261–3270. doi: 10.1093/nar/18.11.3261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kaufman R. J., Murtha P., Davies M. V. Translational efficiency of polycistronic mRNAs and their utilization to express heterologous genes in mammalian cells. EMBO J. 1987 Jan;6(1):187–193. doi: 10.1002/j.1460-2075.1987.tb04737.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kawahara R. S., Deuel T. F. Platelet-derived growth factor-inducible gene JE is a member of a family of small inducible genes related to platelet factor 4. J Biol Chem. 1989 Jan 15;264(2):679–682. [PubMed] [Google Scholar]
  12. Kleinerman E. S., Zwelling L. A., Howser D., Barlock A., Young R. C., Decker J. M., Bull J., Muchmore A. V. Defective monocyte killing in patients with malignancies and restoration of function during chemotherapy. Lancet. 1980 Nov 22;2(8204):1102–1105. doi: 10.1016/s0140-6736(80)92540-4. [DOI] [PubMed] [Google Scholar]
  13. Kriegler M., Perez C., DeFay K., Albert I., Lu S. D. A novel form of TNF/cachectin is a cell surface cytotoxic transmembrane protein: ramifications for the complex physiology of TNF. Cell. 1988 Apr 8;53(1):45–53. doi: 10.1016/0092-8674(88)90486-2. [DOI] [PubMed] [Google Scholar]
  14. Leonard E. J., Yoshimura T. Human monocyte chemoattractant protein-1 (MCP-1). Immunol Today. 1990 Mar;11(3):97–101. doi: 10.1016/0167-5699(90)90035-8. [DOI] [PubMed] [Google Scholar]
  15. Luster A. D., Jhanwar S. C., Chaganti R. S., Kersey J. H., Ravetch J. V. Interferon-inducible gene maps to a chromosomal band associated with a (4;11) translocation in acute leukemia cells. Proc Natl Acad Sci U S A. 1987 May;84(9):2868–2871. doi: 10.1073/pnas.84.9.2868. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Matsushima K., Larsen C. G., DuBois G. C., Oppenheim J. J. Purification and characterization of a novel monocyte chemotactic and activating factor produced by a human myelomonocytic cell line. J Exp Med. 1989 Apr 1;169(4):1485–1490. doi: 10.1084/jem.169.4.1485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Old L. J. Tumor necrosis factor (TNF). Science. 1985 Nov 8;230(4726):630–632. doi: 10.1126/science.2413547. [DOI] [PubMed] [Google Scholar]
  18. Peveri P., Walz A., Dewald B., Baggiolini M. A novel neutrophil-activating factor produced by human mononuclear phagocytes. J Exp Med. 1988 May 1;167(5):1547–1559. doi: 10.1084/jem.167.5.1547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Richmond A., Balentien E., Thomas H. G., Flaggs G., Barton D. E., Spiess J., Bordoni R., Francke U., Derynck R. Molecular characterization and chromosomal mapping of melanoma growth stimulatory activity, a growth factor structurally related to beta-thromboglobulin. EMBO J. 1988 Jul;7(7):2025–2033. doi: 10.1002/j.1460-2075.1988.tb03042.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Rollins B. J., Morrison E. D., Stiles C. D. Cloning and expression of JE, a gene inducible by platelet-derived growth factor and whose product has cytokine-like properties. Proc Natl Acad Sci U S A. 1988 Jun;85(11):3738–3742. doi: 10.1073/pnas.85.11.3738. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Rollins B. J., Stier P., Ernst T., Wong G. G. The human homolog of the JE gene encodes a monocyte secretory protein. Mol Cell Biol. 1989 Nov;9(11):4687–4695. doi: 10.1128/mcb.9.11.4687. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Schröder J. M., Mrowietz U., Morita E., Christophers E. Purification and partial biochemical characterization of a human monocyte-derived, neutrophil-activating peptide that lacks interleukin 1 activity. J Immunol. 1987 Nov 15;139(10):3474–3483. [PubMed] [Google Scholar]
  23. Smith A., Lalley P. A., Killary A. M., Ghosh-Choudhury G., Wang L. M., Han E. S., Martinez L., Naylor S. L., Sakaguchi A. Y. Sigje, a member of the small inducible gene family that includes platelet factor 4 and melanoma growth stimulatory activity, is on mouse chromosome 11. Cytogenet Cell Genet. 1989;52(3-4):194–196. doi: 10.1159/000132876. [DOI] [PubMed] [Google Scholar]
  24. Tepper R. I., Pattengale P. K., Leder P. Murine interleukin-4 displays potent anti-tumor activity in vivo. Cell. 1989 May 5;57(3):503–512. doi: 10.1016/0092-8674(89)90925-2. [DOI] [PubMed] [Google Scholar]
  25. Urban J. L., Shepard H. M., Rothstein J. L., Sugarman B. J., Schreiber H. Tumor necrosis factor: a potent effector molecule for tumor cell killing by activated macrophages. Proc Natl Acad Sci U S A. 1986 Jul;83(14):5233–5237. doi: 10.1073/pnas.83.14.5233. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Urlaub G., Chasin L. A. Isolation of Chinese hamster cell mutants deficient in dihydrofolate reductase activity. Proc Natl Acad Sci U S A. 1980 Jul;77(7):4216–4220. doi: 10.1073/pnas.77.7.4216. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Valente A. J., Graves D. T., Vialle-Valentin C. E., Delgado R., Schwartz C. J. Purification of a monocyte chemotactic factor secreted by nonhuman primate vascular cells in culture. Biochemistry. 1988 May 31;27(11):4162–4168. doi: 10.1021/bi00411a039. [DOI] [PubMed] [Google Scholar]
  28. Wilson S. D., Billings P. R., D'Eustachio P., Fournier R. E., Geissler E., Lalley P. A., Burd P. R., Housman D. E., Taylor B. A., Dorf M. E. Clustering of cytokine genes on mouse chromosome 11. J Exp Med. 1990 Apr 1;171(4):1301–1314. doi: 10.1084/jem.171.4.1301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Wolpe S. D., Cerami A. Macrophage inflammatory proteins 1 and 2: members of a novel superfamily of cytokines. FASEB J. 1989 Dec;3(14):2565–2573. doi: 10.1096/fasebj.3.14.2687068. [DOI] [PubMed] [Google Scholar]
  30. Yang Y. C., Ciarletta A. B., Temple P. A., Chung M. P., Kovacic S., Witek-Giannotti J. S., Leary A. C., Kriz R., Donahue R. E., Wong G. G. Human IL-3 (multi-CSF): identification by expression cloning of a novel hematopoietic growth factor related to murine IL-3. Cell. 1986 Oct 10;47(1):3–10. doi: 10.1016/0092-8674(86)90360-0. [DOI] [PubMed] [Google Scholar]
  31. Yoshimura T., Matsushima K., Tanaka S., Robinson E. A., Appella E., Oppenheim J. J., Leonard E. J. Purification of a human monocyte-derived neutrophil chemotactic factor that has peptide sequence similarity to other host defense cytokines. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9233–9237. doi: 10.1073/pnas.84.24.9233. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Yoshimura T., Robinson E. A., Tanaka S., Appella E., Kuratsu J., Leonard E. J. Purification and amino acid analysis of two human glioma-derived monocyte chemoattractants. J Exp Med. 1989 Apr 1;169(4):1449–1459. doi: 10.1084/jem.169.4.1449. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Yoshimura T., Yuhki N., Moore S. K., Appella E., Lerman M. I., Leonard E. J. Human monocyte chemoattractant protein-1 (MCP-1). Full-length cDNA cloning, expression in mitogen-stimulated blood mononuclear leukocytes, and sequence similarity to mouse competence gene JE. FEBS Lett. 1989 Feb 27;244(2):487–493. doi: 10.1016/0014-5793(89)80590-3. [DOI] [PubMed] [Google Scholar]
  34. Zachariae C. O., Anderson A. O., Thompson H. L., Appella E., Mantovani A., Oppenheim J. J., Matsushima K. Properties of monocyte chemotactic and activating factor (MCAF) purified from a human fibrosarcoma cell line. J Exp Med. 1990 Jun 1;171(6):2177–2182. doi: 10.1084/jem.171.6.2177. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Molecular and Cellular Biology are provided here courtesy of Taylor & Francis

RESOURCES