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
. 1980 Sep;77(9):5258–5262. doi: 10.1073/pnas.77.9.5258

Transforming growth factors produced by certain human tumor cells: polypeptides that interact with epidermal growth factor receptors.

G J Todaro, C Fryling, J E De Larco
PMCID: PMC350037  PMID: 6254071

Abstract

Three different human tumor lines in culture, a rhabdomyosarcoma, a bronchogenic carcinoma and a metastatic melanoma, release proteins (transforming growth factors, TGFs) into the medium that confer the transformed phenotype on untransformed fibroblasts. These proteins are acid and heat-stable; produce profound morphologic changes in rat and human fibroblasts; and enable normal anchorage-dependent cells to grow in agar. Removal of the transforming protein results in a reversion of cell phenotype. The major activity interacts with epidermal growth factor (EGF) cell membrane receptors. The peptides from these tumor cells are similar in their action to the sarcoma growth factor (SGF) released by murine sarcoma virus-transformed rodent cells. The most anchorage-independent tumor cells released the most TGFs. EGF-related TGFs were not detectable in fluids from cultures of cells with high numbers of free EGF membrane receptors (normal human fibroblasts and human carcinomas).

Full text

PDF
5258

Selected References

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

  1. Carpenter G., King L., Jr, Cohen S. Rapid enhancement of protein phosphorylation in A-431 cell membrane preparations by epidermal growth factor. J Biol Chem. 1979 Jun 10;254(11):4884–4891. [PubMed] [Google Scholar]
  2. Cho H. Y., Rhim J. S. Cycloheximide-dependent reversion of human cells transformed by MSV and chemical carcinogen. Science. 1979 Aug 17;205(4407):691–693. doi: 10.1126/science.223242. [DOI] [PubMed] [Google Scholar]
  3. De Larco J. E., Reynolds R., Carlberg K., Engle C., Todaro G. J. Sarcoma growth factor from mouse sarcoma virus-transformed cells. Purification by binding and elution from epidermal growth factor receptor-rich cells. J Biol Chem. 1980 Apr 25;255(8):3685–3690. [PubMed] [Google Scholar]
  4. Fabricant R. N., De Larco J. E., Todaro G. J. Nerve growth factor receptors on human melanoma cells in culture. Proc Natl Acad Sci U S A. 1977 Feb;74(2):565–569. doi: 10.1073/pnas.74.2.565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. GREENWOOD F. C., HUNTER W. M., GLOVER J. S. THE PREPARATION OF I-131-LABELLED HUMAN GROWTH HORMONE OF HIGH SPECIFIC RADIOACTIVITY. Biochem J. 1963 Oct;89:114–123. doi: 10.1042/bj0890114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Giard D. J., Aaronson S. A., Todaro G. J., Arnstein P., Kersey J. H., Dosik H., Parks W. P. In vitro cultivation of human tumors: establishment of cell lines derived from a series of solid tumors. J Natl Cancer Inst. 1973 Nov;51(5):1417–1423. doi: 10.1093/jnci/51.5.1417. [DOI] [PubMed] [Google Scholar]
  7. Haigler H., Ash J. F., Singer S. J., Cohen S. Visualization by fluorescence of the binding and internalization of epidermal growth factor in human carcinoma cells A-431. Proc Natl Acad Sci U S A. 1978 Jul;75(7):3317–3321. doi: 10.1073/pnas.75.7.3317. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Huu Duc-Nguyen, Rosenblum E. N., Zeigel R. F. Persistent infection of a rat kidney cell line with Rauscher murine leukemia virus. J Bacteriol. 1966 Oct;92(4):1133–1140. doi: 10.1128/jb.92.4.1133-1140.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Keski-Oja J., de Larco J. E., Rapp U. R., Todaro G. J. Murine sarcoma growth factors affect the growth and morphology of cultured mouse epithelial cells. J Cell Physiol. 1980 Jul;104(1):41–46. doi: 10.1002/jcp.1041040107. [DOI] [PubMed] [Google Scholar]
  10. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  11. Montesano R., Drevon C., Kuroki T., Saint Vincent L., Handleman S., Sanford K. K., DeFeo D., Weinstein I. B. Test for malignant transformation of rat liver cells in culture: cytology, growth in soft agar, and production of plasminogen activator. J Natl Cancer Inst. 1977 Dec;59(6):1651–1658. doi: 10.1093/jnci/59.6.1651. [DOI] [PubMed] [Google Scholar]
  12. Nexø E., Hollenberg M. D., Figueroa A., Pratt R. M. Detection of epidermal growth factor-urogastrone and its receptor during fetal mouse development. Proc Natl Acad Sci U S A. 1980 May;77(5):2782–2785. doi: 10.1073/pnas.77.5.2782. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Rinderknecht E., Humbel R. E. The amino acid sequence of human insulin-like growth factor I and its structural homology with proinsulin. J Biol Chem. 1978 Apr 25;253(8):2769–2776. [PubMed] [Google Scholar]
  14. Roberts A. B., Lamb L. C., Newton D. L., Sporn M. B., De Larco J. E., Todaro G. J. Transforming growth factors: isolation of polypeptides from virally and chemically transformed cells by acid/ethanol extraction. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3494–3498. doi: 10.1073/pnas.77.6.3494. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Savage C. R., Jr, Cohen S. Epidermal growth factor and a new derivative. Rapid isolation procedures and biological and chemical characterization. J Biol Chem. 1972 Dec 10;247(23):7609–7611. [PubMed] [Google Scholar]
  16. Sherwin S. A., Sliski A. H., Todaro G. J. Human melanoma cells have both nerve growth factor and nerve growth factor-specific receptors on their cell surfaces. Proc Natl Acad Sci U S A. 1979 Mar;76(3):1288–1292. doi: 10.1073/pnas.76.3.1288. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Shin S. I., Freedman V. H., Risser R., Pollack R. Tumorigenicity of virus-transformed cells in nude mice is correlated specifically with anchorage independent growth in vitro. Proc Natl Acad Sci U S A. 1975 Nov;72(11):4435–4439. doi: 10.1073/pnas.72.11.4435. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Todaro G. J., De Larco J. E. Growth factors produced by sarcoma virus-transformed cells. Cancer Res. 1978 Nov;38(11 Pt 2):4147–4154. [PubMed] [Google Scholar]
  19. de Larco J. E., Todaro G. J. Epithelioid and fibroblastic rat kidney cell clones: epidermal growth factor (EGF) receptors and the effect of mouse sarcoma virus transformation. J Cell Physiol. 1978 Mar;94(3):335–342. doi: 10.1002/jcp.1040940311. [DOI] [PubMed] [Google Scholar]
  20. de Larco J. E., Todaro G. J. Growth factors from murine sarcoma virus-transformed cells. Proc Natl Acad Sci U S A. 1978 Aug;75(8):4001–4005. doi: 10.1073/pnas.75.8.4001. [DOI] [PMC free article] [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