Skip to main content
Log in

The potential role of the heparin-binding growth factor pleiotrophin in breast cancer

  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Summary

We propose that the secreted protein pleiotrophin (PTN) is a major factor in the malignant progression of breast cancer. This hypothesis is based on the growth-stimulatory effects of PTN on cellsin vitro andin vivo and on its high levels of expression in 60% of tumor samples from breast cancer patients. The stimulation of proliferation and tube formation of endothelial cells by PTN suggests that it can serve as an angiogenesis factor during tumor growth. We hypothesize that PTN has the potential to support growth of breast cancer at its primary site and to enhance the ability of tumor cells to metastasize. Furthermore, we suggest that specific endocrine signals interact to regulate the expression of PTNin vitro andin vivo. Finally, we propose that understanding the functions of PTN and its hormonal regulation can lead to the development of novel therapeutic strategies for breast cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Cross M, Dexter TM: Growth factors in development, transformation, and tumorigenesis. Cell 64: 271–280, 1991

    Google Scholar 

  2. Liotta LA, Steeg PS, Stetler-Stevenson WG: Cancer metastasis and angiogenesis: An imbalance of positive and negative regulation. Cell 64: 327–336, 1991

    Google Scholar 

  3. Dickson R, Lippman ME: Estrogenic regulation of growth and polypeptide growth factor secretion in human breast carcinoma. Endocr Rev 8: 29–43, 1987

    Google Scholar 

  4. Wellstein A, Lippman ME: Fibroblast growth factors and breast cancer. In: Broder S (ed) Molecular Foundations of Oncology. Williams and Wilkins, Baltimore, 1991, pp 403–418

    Google Scholar 

  5. Clarke R, Dickson RB, Lippman ME: Hormonal aspects of breast cancer. Growth factors, drugs and stromal interactions. Crit Rev Oncol Hematol 12: 1–23, 1992

    Google Scholar 

  6. Dickson RB, McManaway ME, Lippman ME: Estrogen-induced factors of breast cancer cells partially replace estrogen to promote tumor growth. Science 232: 1540–1543, 1986

    Google Scholar 

  7. Knabbe C, Lippman ME, Wakefield LM,et al.: Evidence that transforming growth factor beta is a hormonally regulated negative growth factor in human breast cancer cells. Cell 48: 417–428, 1987

    Google Scholar 

  8. Huff KK, Knabbe C, Lindsey R,et al.: Multihormonal regulation of insulin-like growth factor-I-related protein in MCF-7 human breast cancer cells. Mol Endocrinol 2: 200–208, 1988

    Google Scholar 

  9. Dickson RB, Huff KK, Spencer EM, Lippman ME: Induction of epidermal growth factor-related polypeptides by 17 beta-estradiol in MCF-7 human breast cancer cells. Endocrinology 118: 138–142, 1986

    Google Scholar 

  10. Kadomatsu K, Huang RP, Suganuma T, Murata F, Muramatsu T: A retinoic acid responsive gene MK found in the teratocarcinoma system is expressed in spatially and temporally controlled manner during mouse embryogenesis. J Cell Biol 110: 607–616, 1990

    Google Scholar 

  11. Böhlen P, Kovesdi I: HBNF and MK, members of a novel gene family of heparin-binding proteins with potential roles in embryogenesis and brain function. Prog Growth Factor Res 3: 143–157, 1991

    Google Scholar 

  12. Courty J, Dauchel MC, Caruelle D, Nguyen TT, Barritault D: Purification and characterization of a new endothelial cell growth factor named HARP (Heparin Affin Regulatory Peptide). J Cell Biochem 15F: Abstr. 221, 1991 (abstract)

    Google Scholar 

  13. Courty J, Dauchel MC, Caruelle D, Perderiset M, Barritault D: Mitogenic properties of a new endothelial cell growth factor related to pleiotrophin. Biochem Biophys Res Commun 180: 145–151, 1991

    Google Scholar 

  14. Kovesdi I, Fairhurst JL, Kretschmer PJ, Böhlen P: Heparinbinding neurotrophic factor (HBNF) and MK, members of a new family of homologous, developmentally regulated proteins. Biochem Biophys Res Commun 172: 850–854, 1990

    Google Scholar 

  15. Huber D, Gautschi-Sova P, Böhlen P: Amino-terminal sequences of a novel heparin-binding protein from human, bovine, rat, and chick brain: high interspecies homology. Neurochem Res 15: 435–439, 1990

    Google Scholar 

  16. Kuo MD, Oda Y, Huang JS, Huang SS: Amino acid sequence and characterization of a heparin-binding neurite-promoting factor (p18) from bovine brain. J Biol Chem 265: 18749–18752, 1990

    Google Scholar 

  17. Rauvala H: An 18-kd heparin-binding protein of developing brain that is distinct from fibroblast growth factors. EMBO J 8: 2933–2941, 1989

    Google Scholar 

  18. Merenmies J, Rauvala H: Molecular cloning of the 18-kDa growth-associated protein of developing brain. J Biol Chem 265: 16721–16724, 1990

    Google Scholar 

  19. Milner PG, Li YS, Hoffman RM, Kodner CM, Siegel NR, Deuel TF: A novel 17 kD heparin-binding growth factor (HBGF-8) in bovine uterus: purification and N-terminal amino acid sequence. Biochem Biophys Res Commun 165: 1096–1103, 1989

    Google Scholar 

  20. Tezuka K, Takeshita S, Hakeda Y, Kumegawa M, Kikuno R, Hashimoto-Gotoh T: Isolation of mouse and human cDNA clones encoding a protein expressed specifically in osteoblasts and brain tissues. Biochem Biophys Res Commun 173: 246–251, 1990

    Google Scholar 

  21. Li YS, Milner PG, Chauhan AK,et al.: Cloning and expression of a developmentally regulated protein that induces mitogenic and neurite outgrowth activity. Science 250: 1690–1694, 1990

    Google Scholar 

  22. Wellstein A, Fang WJ, Khatri A,et al.: A heparin-binding growth factor secreted from breast cancer cells homologous to a developmentally regulated cytokine. J Biol Chem 267: 2582–2587, 1992

    Google Scholar 

  23. Hampton BS, Marshak DR, Burgess WH: Structural and functional characterization of full-length heparin-binding growth associated molecule. Mol Biol Cell 3: 85–93, 1992

    Google Scholar 

  24. Raulo E, Julkunen I, Merenmies J, Pihlaskari R, Rauvala H: Secretion and biological activities of heparin-binding growth-associated molecule. J Biol Chem 267: 11408–11416, 1992

    Google Scholar 

  25. Takamatsu H, Itoh M, Kimura M, Gospodarowicz D, Amann E: Expression and purification of biologically active human OSF-1 inEscherichia coli. Biochem Biophys Res Commun 185: 224–230, 1992

    Google Scholar 

  26. Fang WJ, Hartmann N, Chow D, Riegel AT, Wellstein A: Pleiotrophin stimulates fibroblasts, endothelial and epithelial cells, and is expressed in human cancer. J Biol Chem 267: 25889–25897, 1992

    Google Scholar 

  27. Lai SP, Czubayko F, Riegel AT, Wellstein A: Structure of the human heparin-binding growth factor gene pleiotrophin. Biochem Biophys Res Commun 187: 1113–1122, 1992

    Google Scholar 

  28. Li YS, Hoffman RM, Le Beau MM,et al.: Characterization of the human pleiotrophin gene. J Biol Chem 267: 26011–26016, 1992

    Google Scholar 

  29. Milner PG, Shah D, Veile R, Donis-Keller H, Kumar BV: Cloning, nucleotide sequence and chromosome localization of the human pleiotrophin gene. Biochemistry 31: 12023–12028, 1992

    Google Scholar 

  30. Li YS, Hoffman RM, Le Beau MM,et al.: Characterization of the human pleiotrophin gene. Promoter region and chromosomal localization. J Biol Chem 267: 26011–26016, 1992

    Google Scholar 

  31. Kretschmer PJ, Fairhurst JL, Hulmes JD, Popjes ML, Böhlen P, Kovesdi I: Genomic organization of the human HBNF gene and characterization of an HBNF variant protein as a splice mutant. Biochem Biophys Res Commun 192: 420–429, 1993

    Google Scholar 

  32. Chauhan AK, Li YS, Deuel TF: Pleiotrophin transforms NIH 3T3 cells and induces tumors in nude mice. Proc Natl Acad Sci USA 90: 679–682, 1993

    Google Scholar 

  33. Segrase J, Marks M, Hirschfeld S,et al.: Inhibition of estrogen responsive gene activation by the retinoid x receptor beta: evidence for multiple inhibitory pathways. Mol Cell Biol 13: 2258–2268, 1993

    Google Scholar 

  34. Gibson DF, Gottardis MM, Jordan VC: Sensitivity and insensitivity of breast cancer to tamoxifen. J Steroid Biochem Mol Biol 37: 765–770, 1990

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tate Riegel, A., Wellstein, A. The potential role of the heparin-binding growth factor pleiotrophin in breast cancer. Breast Cancer Res Tr 31, 309–314 (1994). https://doi.org/10.1007/BF00666163

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00666163

Keywords

Navigation