Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1995 May 9;92(10):4562–4566. doi: 10.1073/pnas.92.10.4562

Interferons alpha and beta down-regulate the expression of basic fibroblast growth factor in human carcinomas.

R K Singh 1, M Gutman 1, C D Bucana 1, R Sanchez 1, N Llansa 1, I J Fidler 1
PMCID: PMC41984  PMID: 7753843

Abstract

We investigated the influence of interferons alpha, beta, and gamma (IFN-alpha, -beta, and -gamma) on the production of basic fibroblast growth factor (bFGF) by human renal carcinoma cells. The human renal carcinoma cell metastatic line SN12PM6 was established in culture from a lung metastasis and SN12PM6-resistant cells were selected in vitro for resistance to the antiproliferative effects of IFN-alpha or IFN-beta. IFN-alpha and IFN-beta, but not IFN-gamma, down-regulated the expression of bFGF at the mRNA and protein levels by a mechanism independent of their antiproliferative effects. Down-regulation of bFGF required a long exposure (> 4 days) of cells to low concentrations (> 10 units/ml) of IFN-alpha or IFN-beta. The withdrawal of IFN-alpha or IFN-beta from the medium permitted SN12PM6-resistant cells to resume production of bFGF. The incubation of human bladder, prostate, colon, and breast carcinoma cells with noncytostatic concentrations of IFN-alpha or IFN-beta also produced down-regulation of bFGF production.

Full text

PDF
4562

Images in this article

4563Fig. 1
on p.4563
4564Fig. 2
on p.4564
4565Fig. 3
on p.4565
4565Fig. 4
on p.4565

Selected References

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

  1. Abraham J. A., Mergia A., Whang J. L., Tumolo A., Friedman J., Hjerrild K. A., Gospodarowicz D., Fiddes J. C. Nucleotide sequence of a bovine clone encoding the angiogenic protein, basic fibroblast growth factor. Science. 1986 Aug 1;233(4763):545–548. doi: 10.1126/science.2425435. [DOI] [PubMed] [Google Scholar]
  2. Alley M. C., Scudiero D. A., Monks A., Hursey M. L., Czerwinski M. J., Fine D. L., Abbott B. J., Mayo J. G., Shoemaker R. H., Boyd M. R. Feasibility of drug screening with panels of human tumor cell lines using a microculture tetrazolium assay. Cancer Res. 1988 Feb 1;48(3):589–601. [PubMed] [Google Scholar]
  3. Bucana C. D., Radinsky R., Dong Z., Sanchez R., Brigati D. J., Fidler I. J. A rapid colorimetric in situ mRNA hybridization technique using hyperbiotinylated oligonucleotide probes for analysis of mdr1 in mouse colon carcinoma cells. J Histochem Cytochem. 1993 Apr;41(4):499–506. doi: 10.1177/41.4.8095509. [DOI] [PubMed] [Google Scholar]
  4. Burgess W. H., Maciag T. The heparin-binding (fibroblast) growth factor family of proteins. Annu Rev Biochem. 1989;58:575–606. doi: 10.1146/annurev.bi.58.070189.003043. [DOI] [PubMed] [Google Scholar]
  5. Dvorak H. F., Gresser I. Microvascular injury in pathogenesis of interferon-induced necrosis of subcutaneous tumors in mice. J Natl Cancer Inst. 1989 Apr 5;81(7):497–502. doi: 10.1093/jnci/81.7.497. [DOI] [PubMed] [Google Scholar]
  6. Ezekowitz R. A., Mulliken J. B., Folkman J. Interferon alfa-2a therapy for life-threatening hemangiomas of infancy. N Engl J Med. 1992 May 28;326(22):1456–1463. doi: 10.1056/NEJM199205283262203. [DOI] [PubMed] [Google Scholar]
  7. Fabra A., Nakajima M., Bucana C. D., Fidler I. J. Modulation of the invasive phenotype of human colon carcinoma cells by organ specific fibroblasts of nude mice. Differentiation. 1992 Dec;52(1):101–110. doi: 10.1111/j.1432-0436.1992.tb00504.x. [DOI] [PubMed] [Google Scholar]
  8. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  9. Fidler I. J. Critical factors in the biology of human cancer metastasis: twenty-eighth G.H.A. Clowes memorial award lecture. Cancer Res. 1990 Oct 1;50(19):6130–6138. [PubMed] [Google Scholar]
  10. Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med. 1995 Jan;1(1):27–31. doi: 10.1038/nm0195-27. [DOI] [PubMed] [Google Scholar]
  11. Folkman J., Klagsbrun M. Angiogenic factors. Science. 1987 Jan 23;235(4787):442–447. doi: 10.1126/science.2432664. [DOI] [PubMed] [Google Scholar]
  12. Folkman J. The role of angiogenesis in tumor growth. Semin Cancer Biol. 1992 Apr;3(2):65–71. [PubMed] [Google Scholar]
  13. Fort P., Marty L., Piechaczyk M., el Sabrouty S., Dani C., Jeanteur P., Blanchard J. M. Various rat adult tissues express only one major mRNA species from the glyceraldehyde-3-phosphate-dehydrogenase multigenic family. Nucleic Acids Res. 1985 Mar 11;13(5):1431–1442. doi: 10.1093/nar/13.5.1431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gohji K., Nakajima M., Fabra A., Bucana C. D., von Eschenbach A. C., Tsuruo T., Fidler I. J. Regulation of gelatinase production in metastatic renal cell carcinoma by organ-specific fibroblasts. Jpn J Cancer Res. 1994 Feb;85(2):152–160. doi: 10.1111/j.1349-7006.1994.tb02076.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gutterman J. U. Cytokine therapeutics: lessons from interferon alpha. Proc Natl Acad Sci U S A. 1994 Feb 15;91(4):1198–1205. doi: 10.1073/pnas.91.4.1198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Harris E. D., Jr Rheumatoid arthritis. Pathophysiology and implications for therapy. N Engl J Med. 1990 May 3;322(18):1277–1289. doi: 10.1056/NEJM199005033221805. [DOI] [PubMed] [Google Scholar]
  17. Killion J. J., Fan D., Bucana C. D., Frangos D. N., Price J. E., Fidler I. J. Augmentation of antiproliferative activity of interferon alfa against human bladder tumor cell lines by encapsulation of interferon alfa within liposomes. J Natl Cancer Inst. 1989 Sep 20;81(18):1387–1392. doi: 10.1093/jnci/81.18.1387. [DOI] [PubMed] [Google Scholar]
  18. Morikawa K., Walker S. M., Nakajima M., Pathak S., Jessup J. M., Fidler I. J. Influence of organ environment on the growth, selection, and metastasis of human colon carcinoma cells in nude mice. Cancer Res. 1988 Dec 1;48(23):6863–6871. [PubMed] [Google Scholar]
  19. Mydlo J. H., Heston W. D., Fair W. R. Characterization of a heparin-binding growth factor from adenocarcinoma of the kidney. J Urol. 1988 Dec;140(6):1575–1579. doi: 10.1016/s0022-5347(17)42130-6. [DOI] [PubMed] [Google Scholar]
  20. Naito S., von Eschenbach A. C., Giavazzi R., Fidler I. J. Growth and metastasis of tumor cells isolated from a human renal cell carcinoma implanted into different organs of nude mice. Cancer Res. 1986 Aug;46(8):4109–4115. [PubMed] [Google Scholar]
  21. Nanus D. M., Schmitz-Dräger B. J., Motzer R. J., Lee A. C., Vlamis V., Cordon-Cardo C., Albino A. P., Reuter V. E. Expression of basic fibroblast growth factor in primary human renal tumors: correlation with poor survival. J Natl Cancer Inst. 1993 Oct 6;85(19):1597–1599. doi: 10.1093/jnci/85.19.1597. [DOI] [PubMed] [Google Scholar]
  22. Nguyen M., Watanabe H., Budson A. E., Richie J. P., Hayes D. F., Folkman J. Elevated levels of an angiogenic peptide, basic fibroblast growth factor, in the urine of patients with a wide spectrum of cancers. J Natl Cancer Inst. 1994 Mar 2;86(5):356–361. doi: 10.1093/jnci/86.5.356. [DOI] [PubMed] [Google Scholar]
  23. Plouët J., Gospodarowicz D. Transforming growth factor beta-1 positively modulates the bioactivity of fibroblast growth factor on corneal endothelial cells. J Cell Physiol. 1989 Nov;141(2):392–399. doi: 10.1002/jcp.1041410221. [DOI] [PubMed] [Google Scholar]
  24. Radinsky R., Bucana C. D., Ellis L. M., Sanchez R., Cleary K. R., Brigati D. J., Fidler I. J. A rapid colorimetric in situ messenger RNA hybridization technique for analysis of epidermal growth factor receptor in paraffin-embedded surgical specimens of human colon carcinomas. Cancer Res. 1993 Mar 1;53(5):937–943. [PubMed] [Google Scholar]
  25. Radinsky R., Kraemer P. M., Raines M. A., Kung H. J., Culp L. A. Amplification and rearrangement of the Kirsten ras oncogene in virus-transformed BALB/c 3T3 cells during malignant tumor progression. Proc Natl Acad Sci U S A. 1987 Aug;84(15):5143–5147. doi: 10.1073/pnas.84.15.5143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Real F. X., Oettgen H. F., Krown S. E. Kaposi's sarcoma and the acquired immunodeficiency syndrome: treatment with high and low doses of recombinant leukocyte A interferon. J Clin Oncol. 1986 Apr;4(4):544–551. doi: 10.1200/JCO.1986.4.4.544. [DOI] [PubMed] [Google Scholar]
  27. Rogelj S., Weinberg R. A., Fanning P., Klagsbrun M. Basic fibroblast growth factor fused to a signal peptide transforms cells. Nature. 1988 Jan 14;331(6152):173–175. doi: 10.1038/331173a0. [DOI] [PubMed] [Google Scholar]
  28. Sidky Y. A., Borden E. C. Inhibition of angiogenesis by interferons: effects on tumor- and lymphocyte-induced vascular responses. Cancer Res. 1987 Oct 1;47(19):5155–5161. [PubMed] [Google Scholar]
  29. Singh R. K., Bucana C. D., Gutman M., Fan D., Wilson M. R., Fidler I. J. Organ site-dependent expression of basic fibroblast growth factor in human renal cell carcinoma cells. Am J Pathol. 1994 Aug;145(2):365–374. [PMC free article] [PubMed] [Google Scholar]
  30. Stephenson R. A., Dinney C. P., Gohji K., Ordóez N. G., Killion J. J., Fidler I. J. Metastatic model for human prostate cancer using orthotopic implantation in nude mice. J Natl Cancer Inst. 1992 Jun 17;84(12):951–957. doi: 10.1093/jnci/84.12.951. [DOI] [PubMed] [Google Scholar]
  31. Vlodavsky I., Korner G., Ishai-Michaeli R., Bashkin P., Bar-Shavit R., Fuks Z. Extracellular matrix-resident growth factors and enzymes: possible involvement in tumor metastasis and angiogenesis. Cancer Metastasis Rev. 1990 Nov;9(3):203–226. doi: 10.1007/BF00046361. [DOI] [PubMed] [Google Scholar]
  32. Weidner N., Carroll P. R., Flax J., Blumenfeld W., Folkman J. Tumor angiogenesis correlates with metastasis in invasive prostate carcinoma. Am J Pathol. 1993 Aug;143(2):401–409. [PMC free article] [PubMed] [Google Scholar]
  33. White C. W., Sondheimer H. M., Crouch E. C., Wilson H., Fan L. L. Treatment of pulmonary hemangiomatosis with recombinant interferon alfa-2a. N Engl J Med. 1989 May 4;320(18):1197–1200. doi: 10.1056/NEJM198905043201807. [DOI] [PubMed] [Google Scholar]
  34. Zhang R. D., Fidler I. J., Price J. E. Relative malignant potential of human breast carcinoma cell lines established from pleural effusions and a brain metastasis. Invasion Metastasis. 1991;11(4):204–215. [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES