Skip to main content
PMC 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
. 1989 Oct;86(19):7427–7431. doi: 10.1073/pnas.86.19.7427

Production of platelet-derived endothelial cell growth factor by normal and transformed human cells in culture.

K Usuki 1, N E Heldin 1, K Miyazono 1, F Ishikawa 1, F Takaku 1, B Westermark 1, C H Heldin 1
PMCID: PMC298077  PMID: 2678104

Abstract

Platelet-derived endothelial cell growth factor (PD-ECGF) is a 45-kDa endothelial cell mitogen which has angiogenic properties in vivo. We report here that human foreskin fibroblasts, a human squamous cell carcinoma cell line, and 2 out of the 3 human thyroid carcinoma cell lines investigated produce PD-ECGF, whereas 21 other cell lines examined do not. The positive cell lines contained a 1.8-kilobase PD-ECGF mRNA, and a 45-kDa protein could be demonstrated in lysates of the cell lines by immunoblotting and immunoprecipitation using a specific antiserum against PD-ECGF. Furthermore, the cell lysates contained mitogenic activity for endothelial cells that was neutralized by the PD-ECGF antiserum. PD-ECGF was found to be secreted only slowly from the producer cells, consistent with the previous finding that the primary translation product lacks a signal sequence. The restricted expression and intracellular sequestration of PD-ECGF imply a strictly controlled function in endothelial cell proliferation and angiogenesis. Aberrant production of PD-ECGF may play a role in tumor angiogenesis.

Full text

PDF
7427

Images in this article

7428Image
on p.7428
7428Image
on p.7428
7429Image
on p.7429
7429Image
on p.7429

Selected References

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

  1. Abraham J. A., Whang J. L., Tumolo A., Mergia A., Friedman J., Gospodarowicz D., Fiddes J. C. Human basic fibroblast growth factor: nucleotide sequence and genomic organization. EMBO J. 1986 Oct;5(10):2523–2528. doi: 10.1002/j.1460-2075.1986.tb04530.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Auffray C., Rougeon F. Purification of mouse immunoglobulin heavy-chain messenger RNAs from total myeloma tumor RNA. Eur J Biochem. 1980 Jun;107(2):303–314. doi: 10.1111/j.1432-1033.1980.tb06030.x. [DOI] [PubMed] [Google Scholar]
  3. Blobel G., Dobberstein B. Transfer of proteins across membranes. I. Presence of proteolytically processed and unprocessed nascent immunoglobulin light chains on membrane-bound ribosomes of murine myeloma. J Cell Biol. 1975 Dec;67(3):835–851. doi: 10.1083/jcb.67.3.835. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Folkman J., Klagsbrun M. Angiogenic factors. Science. 1987 Jan 23;235(4787):442–447. doi: 10.1126/science.2432664. [DOI] [PubMed] [Google Scholar]
  5. Fox G. M., Schiffer S. G., Rohde M. F., Tsai L. B., Banks A. R., Arakawa T. Production, biological activity, and structure of recombinant basic fibroblast growth factor and an analog with cysteine replaced by serine. J Biol Chem. 1988 Dec 5;263(34):18452–18458. [PubMed] [Google Scholar]
  6. Gospodarowicz D., Neufeld G., Schweigerer L. Fibroblast growth factor. Mol Cell Endocrinol. 1986 Aug;46(3):187–204. doi: 10.1016/0303-7207(86)90001-8. [DOI] [PubMed] [Google Scholar]
  7. Huang S. S., Huang J. S. Association of bovine brain-derived growth factor receptor with protein tyrosine kinase activity. J Biol Chem. 1986 Jul 25;261(21):9568–9571. [PubMed] [Google Scholar]
  8. Ishikawa F., Miyazono K., Hellman U., Drexler H., Wernstedt C., Hagiwara K., Usuki K., Takaku F., Risau W., Heldin C. H. Identification of angiogenic activity and the cloning and expression of platelet-derived endothelial cell growth factor. Nature. 1989 Apr 13;338(6216):557–562. doi: 10.1038/338557a0. [DOI] [PubMed] [Google Scholar]
  9. Jaye M., Howk R., Burgess W., Ricca G. A., Chiu I. M., Ravera M. W., O'Brien S. J., Modi W. S., Maciag T., Drohan W. N. Human endothelial cell growth factor: cloning, nucleotide sequence, and chromosome localization. Science. 1986 Aug 1;233(4763):541–545. doi: 10.1126/science.3523756. [DOI] [PubMed] [Google Scholar]
  10. Mark J., Ekedahl C., Dahlenfors R., Westermark B. Cytogenetical observations in five human anaplastic thyroid carcinomas. Hereditas. 1987;107(2):163–174. doi: 10.1111/j.1601-5223.1987.tb00281.x. [DOI] [PubMed] [Google Scholar]
  11. Miyazono K., Heldin C. H. High-yield purification of platelet-derived endothelial cell growth factor: structural characterization and establishment of a specific antiserum. Biochemistry. 1989 Feb 21;28(4):1704–1710. doi: 10.1021/bi00430a042. [DOI] [PubMed] [Google Scholar]
  12. Miyazono K., Okabe T., Urabe A., Takaku F., Heldin C. H. Purification and properties of an endothelial cell growth factor from human platelets. J Biol Chem. 1987 Mar 25;262(9):4098–4103. [PubMed] [Google Scholar]
  13. Pontén J., Saksela E. Two established in vitro cell lines from human mesenchymal tumours. Int J Cancer. 1967 Sep 15;2(5):434–447. doi: 10.1002/ijc.2910020505. [DOI] [PubMed] [Google Scholar]
  14. Tso J. Y., Sun X. H., Kao T. H., Reece K. S., Wu R. Isolation and characterization of rat and human glyceraldehyde-3-phosphate dehydrogenase cDNAs: genomic complexity and molecular evolution of the gene. Nucleic Acids Res. 1985 Apr 11;13(7):2485–2502. doi: 10.1093/nar/13.7.2485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Vlodavsky I., Folkman J., Sullivan R., Fridman R., Ishai-Michaeli R., Sasse J., Klagsbrun M. Endothelial cell-derived basic fibroblast growth factor: synthesis and deposition into subendothelial extracellular matrix. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2292–2296. doi: 10.1073/pnas.84.8.2292. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Westermark B. The deficient density-dependent growth control of human malignant glioma cells and virus-transformed glia-like cells in culture. Int J Cancer. 1973 Sep 15;12(2):438–451. doi: 10.1002/ijc.2910120215. [DOI] [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