Growth Factors for Hormone-Sensitive Tumor Cells

  • David A. Sirbasku
  • Frances E. Leland


The study of polypeptide growth factor interaction with cells in vitro and in vivo is a rapidly expanding new field of cell biology. Many types of cell growth factors have been identified including the steroid hormones (1), (4), (33), (65), thyroid hormones (49), (62), prostaglandins (24), (25), the classical polypeptide hormones such as insulin (53), (64), and many polypeptide and protein growth factors. Characterization of the polypeptide growth factors such as epidermal growth factor, EGF (14), (22), (51), nerve growth factor, NGF (2), (32), (68), somatomedins (48), (54), (66), fibroblast growth factor, FGF (19), (20), platelet derived growth factor, PDGF (3), (39), (40), (41), (46), and the insulin-like growth factors, IGF1 and IGF2 (17), (18), (45), have provided us with a detailed analysis of the biochemical properties of growth promoting proteins. These pioneering studies have led the way to two important advances in the growth control field. First, they have provided methods for purifying these activities sufficiently to allow their testing as growth regulatory agents on tissues or cell types not previously recognized as target organs. A case in point is the identification of the effects of EGF on mammary cells (5), (6), (34), (67), a growth factor which initially was believed to promote growth of only the epidermal tissues (14), (51), but is now considered important for growth of several cell types in vivo (11), (12), (44). The second major benefit of characterizing these new mitogens was to provide an impetus to other investigators to seek new growth regulatory polypeptides that may be involved in growth of specialized tissue in vivo.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Allegra J, Lippman ME. Growth of a human breast cancer cell line in serum-free hormone-supplemented medium. Cancer Res 38: 3823–9, 1978.PubMedGoogle Scholar
  2. 2.
    Andres RY, Jeng I, Bradshaw RH. Nerve growth factor receptors: identification of distinct classes in plasma membranes and nuclei of embryonic dorsal root neurons. Proc Natl Acad Sci USA 74: 2785–9, 1977.CrossRefPubMedGoogle Scholar
  3. 3.
    Antoniades HN, Scher C, Stiles C. Purification of human platelet derived growth factor. Proc Natl Acad Sci USA 76: 1809–13, 1979.CrossRefPubMedGoogle Scholar
  4. 4.
    Armelin HA, Armelin MCS, Farios SE, Gambarini AG, Kimura E. Effects of hydrocortisone on the growth control of a mutant derived from Swiss mouse 3T3 fibroblast. pp. 269–279 in Hormones and Cell Culture, Cold Spring Harbor Conferences on Cell Proliferation, eds GH Sato, R Ross. Cold Spring Harbor, New York, 1979.Google Scholar
  5. 5.
    Barnes D, Sato G. Growth of a human mammary tumor cell line in a serum-free medium. Nature 281: 388–9, 1979.CrossRefPubMedGoogle Scholar
  6. 6.
    Barnes D, Sato G. Methods for growth of cultured cells in serum-free medium. Anal Biochem 102: 252–70, 1980.CrossRefGoogle Scholar
  7. 7.
    Bennett DC, Peachey LA, Durbin H, Rudland PS. A possible mammary stem cell line. Cell 15: 283–298, 1978.CrossRefGoogle Scholar
  8. 8.
    Bottenstein J, Hayashi I, Hutchings S, Masui H, Mather J, McClure DB, Ohasa S, Rizzino A, Sato G, Serrero G, Wolf R, Wu R. The growth of cells in serum-free hormone-supplemented media. Methods Enzymol 58: 94–109, 1979.CrossRefPubMedGoogle Scholar
  9. 9.
    Butler WB, Kirkland WL, Gargola TL, Goran H, Kelsey WH. Stimulation of plasminogen activator productions in a human breast cancer cell line (MCF-7) by steroid. J Cell Biol 97 (part 2): 162a, 1980.Google Scholar
  10. 10.
    Byrny RL, Orth DN, Cohen S, Doyne ES. Epidermal growth factor: effects of androgens and adrenergic agents. Endocrinology 95: 776–82, 1974.CrossRefGoogle Scholar
  11. 11.
    Carpenter G, Cohen S. Human epidermal growth factor and the proliferation of human fibroblasts. J Cell Physiol 88: 227–37, 1976.CrossRefPubMedGoogle Scholar
  12. 12.
    Cattertan WZ, Escobedo MB, Sexsan WR, Gray ME, Sundell HW, Stahlman MT. Effect of epidermal growth factor on lung maturation in fetal rabbits. Pediatr Res 13: 104–108, 1979.CrossRefGoogle Scholar
  13. 13.
    Clemmons DR, Van Wyk JJ, Pledger WJ. Sequential addition of platelet factor and plasma to Balb/c 3T3 fibroblast cultures stimulates sowatomedin-c binding early in cell cycle. Proc Natl Acad Sci USA 77: 6644–48, 1980.CrossRefPubMedGoogle Scholar
  14. 14.
    Cohen S, Carpenter G. Human epidermal growth factor: isolation and chemical and biological properties. Proc Natl Acad Sci USA 72: 1317–21, 1975.CrossRefPubMedGoogle Scholar
  15. 15.
    Eastment CT, Sirbasku DA. Platelet derived mammary tumor growth factor. J Cell Physiol 97: 17–27, 1978.CrossRefPubMedGoogle Scholar
  16. 16.
    Eastment CT, Sirbasku DA. Human platelet lysate contains growth factor activities for established cell lines derived from various tissues of several species. In Vitro 16: 694–705, 1980.Google Scholar
  17. 17.
    Froesch ER, Zapf E, Rinderknecht R, Humbel RE. Non-suppressible insulin-like activity (NSILA) from human serum: recent accomplishments and their physiologic implications. Metabolism 27: 1803–28, 1978.CrossRefPubMedGoogle Scholar
  18. 18.
    Froesch ER, Zapf J, Rinderknecht E, Morell B, Schoenle E, Humbel RE. Insulin-like growth factor (IGF-NSILA) structure, function and physiology. pp. 61–77 in Hormones and Cell Culture, Cold Spring Harbor Conferences on Cell Proliferation Vol. 6, eds GH Sato, R Ross. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, 1979.Google Scholar
  19. 19.
    Gospodarowicz D, Rudland P, Lindstrom J, Benirschke K. Fibroblast growth factor (FGF): its localization, purification, mode of action and physiological significance. Adv Metab Disor 8: 302–35, 1975.Google Scholar
  20. 20.
    Gospodarowicz D, Moran JS. Growth factors in mammalian cell culture. Annu Rev Biochem 45: 531–58, 1976.CrossRefPubMedGoogle Scholar
  21. 21.
    Gospodarowicz D, Delgado D, Vlodaysky I. Permissive effect of the extracellular matrix on cell proliferation in vitro. Proc Natl Acad Sci USA 77: 4094–98, 1980.PubMedGoogle Scholar
  22. 22.
    Haigler H, Ash JF, Singer SF, Cohen S. Visualization by fluorescence of the binding and internalization of epidermal growth factor in human carcinoma cells A-431. Proc Natl Acad Sci USA 75: 3317–21, 1978.CrossRefPubMedGoogle Scholar
  23. 23.
    Hayashi I, Sato G. Replacement of serum by hormones permits growth of cells in defined medium. Nature 259: 132–34. 1976.CrossRefPubMedGoogle Scholar
  24. 24.
    Jimenez de Asua L, Clingan D, Rudland PS. Initiation of cell proliferation in cultured mouse fibroblasts by prostaglandin F. Proc Natl Acad Sci USA 72: 2724–28, 1975.CrossRefGoogle Scholar
  25. 25.
    Jimenez de Asua L, Richmond KMU, Otto AM, Kubler AM, O’Farrell MK, Rudland PS. Growth factors and hormones interact in a series of temporal steps to regulate the rate of initiation of DNA synthesis in mouse fibroblasts. pp. 403–424 in Hormones and Cell Culture, Cold Spring Harbor Conferences on Cell Proliferation, Vol 6, eds GH Sato, R Ross, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, 1979.Google Scholar
  26. 26.
    Kano-Sueoka T, Cohen DM, Yamaizumi Z, Nishimura S, Mori M, Fujiki H. Phosphoethanolamine as a growth factor of a mammary carcinoma cell line of rat. Proc Natl Acad Sci USA 76: 5741–44, 1979.CrossRefPubMedGoogle Scholar
  27. 27.
    King RJ, Kaye AM, Shodell MJ. Copurification of an estrogen-induced protein from rat uterus and a factor able to stimulate DNA synthesis in cultured cells. Exp Cell Res 109: 1–8, 1977.CrossRefPubMedGoogle Scholar
  28. 28.
    Kirkland WL, Sorrentino JM, Sirbasku DA. Control of cell growth: III. Direct mitogenic effect of thyroid hormones on an estrogen-dependent rat pituitary tumor cell line. J Natl Cancer Inst 56: 1159–64, 1976.CrossRefPubMedGoogle Scholar
  29. 29.
    Knauer DJ, Iyer AP, Banerjee MR, Smith GL. Identification of somatomedin-like polypeptides produced by mammary tumors of Balb/c mice. Cancer Res 40: 4368–72, 1980.PubMedGoogle Scholar
  30. 30.
    Leland FE, Kohn DF, Sirbasku DA. Uterine luminal fluid growth factors: I. Promotion and inhibition of growth of estrogen-dependent tumor cell lines by factors from rat uterine luminal fluid (unpublished results).Google Scholar
  31. 31.
    Leland FE, Sirbasku DA. Uterine luminal fluid growth factors: II. Biochemical comparisons of rat uterine tissue, plasma and uterine luminal fluid growth promoting and growth inhibiting activities for estrogen-dependent tumor cells (unpublished results).Google Scholar
  32. 32.
    Levi-Montalcini R. Mechanism of action of nerve growth factor. Harvey Lect. 60: 217–59, 1966.PubMedGoogle Scholar
  33. 33.
    Lippman ME, Bolan G, Huff K. The effects of estrogens and anti-estrogens on hormone-responsive human breast cancer in long-term tissue culture. Cancer Res 35: 4595–5601, 1976.Google Scholar
  34. 34.
    Medina D, Oborn CJ. Growth of preneoplastic mammary epithelial cells in serum-free medium. Cancer Res 40: 3982–87, 1980.PubMedGoogle Scholar
  35. 35.
    Middlebrook JL, Dorland RB. Serum effects on the response of mammalian cells to the exotoxins of Pseudomonas aeruginosa and Corynebacterium diphtheria. Can J Microbiol 23: 175–82, 1977.CrossRefPubMedGoogle Scholar
  36. 36.
    Middlebrook JL, Dorland RB. Response of cultured mammalian cells to the exotoxins of Pseudomonas aeruginosa and Corynebacterium diphtheria: differential cytotoxicity. Can J Microbiol 23: 183–89, 1977.CrossRefPubMedGoogle Scholar
  37. 37.
    Mittra I. A novel “cleaved prolactin” in the rat pituitary: part I, biosynthesis, characterization and regulatory control. Biochem Biophys Res Commun 95: 1750–59, 1980.CrossRefPubMedGoogle Scholar
  38. 38.
    Mittra I. A novel “cleaved prolactin” in rat pituitary: part II, in vivo mammary mitogenic activity of its N-terminal 16K moiety. Bio-chem Biophys Res Commun 95: 1760–67, 1980.CrossRefGoogle Scholar
  39. 39.
    Pledger W, Stiles C, Antoniades H, Scher C. Induction of DNA synthesis in Balb/c 3T3 cells by serum components: reevaluation of the commitment process. Proc Natl Acad Sci USA 74: 4481–85, 1977.CrossRefPubMedGoogle Scholar
  40. 40.
    Pledger W, Stiles C, Antoniades H, Scher C. An ordered sequence of events is required before Balb/c 3T3 cells become committed to DNA synthesis. Proc Natl Acad Sci USA 75: 2839–43, 1978.CrossRefPubMedGoogle Scholar
  41. 41.
    Pledger WJ, Wharton W. Regulation of early cell cycle events by serum components. pp. 165–172 in Control Mechanisms in Animal Cells, eds L Jimenez de Asua, R Levi-Montalcini, R Shields, S Iacobelli, Raven Press, New York, 1980.Google Scholar
  42. 42.
    Ptashne K, Hsueh HW, Stockdale FE. Partial purification and characterization of mammary stimulating factor, a protein which promotes proliferation of mammary epithelium. Biochemistry 18: 3533–39, 1979.CrossRefPubMedGoogle Scholar
  43. 43.
    Rajkind M, Gatmartan A, Mackensen S, Giambrone MA, Ponce P, Reid LM. Connective tissue biomatrix: its isolation and utilization for long term cultures of normal rat hepatocytes. J Cell Biol 87: 255–63, 1980.CrossRefGoogle Scholar
  44. 44.
    Reinwald JG, Green H. Serial cultivation of strains of human epidermal kerotinocytes: the formation of keratinizing colonies from single cells. Cell 6: 331–34, 1975.CrossRefGoogle Scholar
  45. 45.
    Rinderknect E, Humbel RE. Primary structure of human insulin-like growth factor II. FEBS letters 89 (2): 283–86, 1978.CrossRefGoogle Scholar
  46. 46.
    Ross R, Biomset J, Kariya B, Harker L. A platelet-dependent serum factor that stimulates the proliferation of arterial smooth muscle cells in vitro. Proc Natl Acad Sci USA 71: 1207–10, 1974.PubMedGoogle Scholar
  47. 47.
    Rowe J, Kasper S. Partial purification and characterization of putative growth factors in extracts of human breast cancer. Endocrinology (supplement) 106: 144, 1980.CrossRefGoogle Scholar
  48. 48.
    Salmon WD Jr, Daughaday WH. A hormonally controlled serum factor which stimulated sulfate incorporation by cartilage in vitro. J Lab Clin Med 49: 825–36, 1957.Google Scholar
  49. 49.
    Samuels HH, Tsai JS, Casanova J. Thyroid hormone action: a cell culture system responsive to physiological concentrations of thyroid hormones. Science 181: 1253–56, 1973.CrossRefPubMedGoogle Scholar
  50. 50.
    Sato G, Reid L. Replacement of serum in cell culture by hormones. Biochem and Mode of Action of Hormones II. 20: 219–31, 1978.Google Scholar
  51. 51.
    Savage CR Jr, Cohen S. Epidermal growth factor and a new derivation. J Biol Chem 247: 7609–11, 1972.PubMedGoogle Scholar
  52. 52.
    Shafie SM. Estrogen and growth of breast cancer: new evidence suggests indirect action. Science 209: 701–2, 1980.CrossRefPubMedGoogle Scholar
  53. 53.
    Shafie SM, Hilf R. Relationship between insulin and estrogen binding to growth responses in 7,12-dimethylbenz[a]anthracene induced rat mammary tumors. Cancer Res 38: 759–64, 1978.PubMedGoogle Scholar
  54. 54.
    Sievestsson H, Frykland L, Uthne K, Hall K, Westermark B. Isolation and chemistry of human somatomedins A and B. Adv Metab Disor 8: 4760, 1975Google Scholar
  55. 55.
    Sirbasku DA. Hormone-responsive growth in vivo of a tissue culture cell line established from the MT-W9A rat mammary tumor. Cancer Res 38: 1154–65, 1978.PubMedGoogle Scholar
  56. 56.
    Sirbasku DA. Estrogen-induction of growth factors specific for hormone-responsive mammary, pituitary and kidney tumor cells. Proc Natl Acad Sci USA 75: 3786–90, 1978.CrossRefPubMedGoogle Scholar
  57. 57.
    Sirbasku DA, Benson RH. Estrogen-inducible growth factors that may act as mediators (estromedins) of estrogen promoted tumor cell growth. pp. 477–97 in Hormones and Cell Culture, Cold Spring Harbor Conferences on Cell Proliferation, Vol. 6, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, 1979.Google Scholar
  58. 58.
    Sirbasku DA, Benson RH. Proposal of an indirect (estromedin) mechanism of estrogen-induced mammary tumor cell growth. pp. 289–314 in Cell Biology of Breast Cancer, eds C McGrath, M Rich, Academic Press, New York, 1981.Google Scholar
  59. 59.
    Sirbasku DA, Kirkland WL. Control of cell growth: IV. Growth properties of a new cell line established from an estrogen-dependent kidney tumor of the Syrian hamster. Endocrinology 95: 1260–72, 1976.CrossRefGoogle Scholar
  60. 60.
    Sirbasku DA, Leland FE, Benson RH. Properties of a growth factor activity present in crude extracts of rat uterus. J Cell Physiol (in press).Google Scholar
  61. 61.
    Sorrentino JM, Kirkland WL, Sirbasku DA. Control of cell growth: I. Estrogen-dependent growth in vivo of a rat pituitary tumor cell line. J Natl Cancer Inst 56: 1149–54, 1976.CrossRefPubMedGoogle Scholar
  62. 62.
    Sorrentino JM, Kirkland WL, Sirbasku DA. Control of cell growth: II. Requirement of thyroid hormones for the in vivo estrogen-dependent growth of rat pituitary tumor cells. J Natl Cancer Inst 56: 1155–58, 1976.CrossRefPubMedGoogle Scholar
  63. 63.
    Soule H, Vazques J, Long A, Albert S, Brennan M. A human cell line from a pleural effusion derived from a breast carcinoma. J Natl Cancer Inst 51: 1409–13, 1973.CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Teng MH, Bartholonew JC, Bissell MJ. Insulin effect on the cell cycly: analysis of the kinetics of growth parameters in confluent chick cells. Proc Natl Acad Sci USA 73: 3173–77, 1976.CrossRefPubMedGoogle Scholar
  65. 65.
    Thrash CR. Cunningham DD. Stimulation of division of density inhibited fibroblasts by glucocorticoid. Nature 242: 399–401, 1973.CrossRefPubMedGoogle Scholar
  66. 66.
    Van Wyk JJ, Underwood LE, Baseman JB, Hintz RL, Clemmons DR, Marshall RN. Exploration of the insulin-like and growth promoting properties of somatomedins by membrane receptor assays. Adv Metab Disor 8: 127–50, 1975.CrossRefGoogle Scholar

Copyright information

© Eden Press Inc. 1982

Authors and Affiliations

  • David A. Sirbasku
  • Frances E. Leland

There are no affiliations available

Personalised recommendations