Journal of Cancer Research and Clinical Oncology

, Volume 119, Issue 11, pp 665–668 | Cite as

Expression of insulin-like growth factor receptors I and II in normal human lung and in lung cancer

  • U. Kaiser
  • C. Schardt
  • D. Brandscheidt
  • E. Wollmer
  • K. Havemann
Original Papers Experimental Oncology


Insulin-like growth factors are potent mitogenic factors in human lung cancer in vitro, acting via specific receptors. Using monoclonal antibodies we demonstrate the expression of insulin-like growth factor receptor I in bronchial epithelial cells of normal lung and in primary lung cancer (22/24 cases), being most prominent in squamous cell carcinoma. Electron microscopy on lung cancer cell lines reveals a distinct reaction pattern on the plasma membrane. Immunoreaction with a specific antibody directed against the insulin-like growth factor receptor II suggests a weak expression in primary lung cancer. Our findings underline the significance of the autocrine pathway of insulin-like growth factors in lung cancer.

Key words

Lung cancer Insulin-like growth factor receptors Immunohistology 



insulin-like growth factor


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Bonneterre J, Peyrat JP, Beuscart R, Demaille A (1990) Prognositic significance of insulin-like growth factor I receptors in human breast cancer. Cancer Res 50:6931–6935PubMedGoogle Scholar
  2. Braulke T, Gartung C, Hasilik A, Figura K von (1987) Is movement of mannose 6-phosphate-specific receptor triggered by binding of lysosomal enzymes? J Cell Biol 104:1735–1742PubMedGoogle Scholar
  3. Braulke T, Causin C, Waheed A, Junghans U, Hasilik A, Maly P, Humbel R, Figura K von (1988) Mannose 6-phosphate/insulin-like growth factor II receptor: distinct binding sites for mannose 6-phosphate and insulin-like growth factor II. Biochem Biophys Res Commun 150:1287–1293PubMedGoogle Scholar
  4. Carnedy DN, Gazdar AF, Bepler G, Guccion JG, Marangos PJ, Moody TW, Zweig MH, Minna JD (1985) Establishment and identification of small cell lung cancer lines having classic and variant features. Cancer Res 45:2913–2923PubMedGoogle Scholar
  5. El-Badry O, Helmann LJ, Chatten J, Steinberg SM, Evabs AE, Israel MA (1991) Insulin-like growth factor II-mediated proliferation of human neuroblastoma. J Clin Invest 87:648–657PubMedGoogle Scholar
  6. Foekens JA, Portengen H, Janssen M, Klijn J (1989) Insulin-like growth factor-I receptors and insulin-like growth factor I like activity in human primary breast cancer. Cancer 63:2139–2147PubMedGoogle Scholar
  7. Furnaletto RW, Di Carlo JN (1984) Somatomedin-C receptors and growth effects in human breast cells maintained in long-term tissue culture. Cancer Res 44:2122–2128PubMedGoogle Scholar
  8. Havemann K, Rotsch M, Schöneberger HJ, Erbil C, Hennig C, Jacques G (1990) Growth regulation by insulin-like growth factors in lung cancer. J Steroid Biochem Mol Biol 37:877–882PubMedGoogle Scholar
  9. Jaques G, Rotsch M, Wegmann C, Worsch U, Maasberg M, Havemann K (1988) Production of immunoreactive insulin-like growth factor I and response to exogenous IGF I in small cell lung cancer cell lines. Exp Cell Res 176:336–343PubMedGoogle Scholar
  10. Kiefer P, Jaques G, Schoeneberger J, Heinrich G, Havemann K (1991) Insulin-like growth factor binding protein expression in human small cell lung cancer cell lines. Exp Cell Res 192:414–417PubMedGoogle Scholar
  11. Kull FC, Jacobs S, Su Y, Svoboda ME, Van Wyk JJ, Cuatrescas P (1983) Monoclonal antibodies to receptors for insulin and somatomedin C. J Biol Chem 228:6561–6565Google Scholar
  12. Macaulay VM, Everard MJ, Teale JD, Trott PA, Van Wyk JJ, Smith IE, Millar JL (1990) Autocrine function for insulin-like growth factor I in human small cell lung cancer cell lines and fresh tumor cells. Cancer Res 50:2511–2517PubMedGoogle Scholar
  13. Minuto F, Del Monte P, Barreca A, Fortini P, Cariola G, Catrambone G, Giordano G (1986) Evidence for an increased somatomedin-C/insulin like growth factor I content in primary human lung tumors. Cancer Res 46:985–988PubMedGoogle Scholar
  14. Morgan DO, Edman JC, Standring DN, Fried VA, Smith MC, Roth RA, Rutter WJ (1987) Insulin-like growth factor II receptor as a multifunctional binding protein. Nature 329:301–307PubMedGoogle Scholar
  15. Nakanishi Y, Mulshine JL, Kaspazyk PG, Natale RB, Maneckjee R, Avis I, Treston AM, Gazdar AF, Minna JD, Cuttita F (1988) Insulin-like growth factor I can mediate autocrine proliferation of human small cell lung cancer cell lines in vivo. J Clin Invest 82:354–359PubMedGoogle Scholar
  16. Osborne CK, Coronado EB, Kitten LJ, Arteaga CI, Fuqua SAW, Ramasharma K, Marshall M, Li CH (1989) Insulin-like growth factor-II (IGF-II): a potential autocrine/paracrine growth factor for human breast cancer acting via the IGF-I receptor. Mol Endocrinol 3:1701–1709PubMedGoogle Scholar
  17. Reynolds ES (1963) The use of lead citrate at high pH as an electronopaque stain in electron microscopy. J Cell Biol 12:207–213Google Scholar
  18. Shigematsu K, Kataoka Y, Kamio T, Kurihara M, Niwa M, Tsuchiyama H (1990) Partial characterization of insulin-like growth factor I in primary human lung cancers using immunohistochemical and receptor autoradiographic technique. Cancer Res 50:2481–2484PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • U. Kaiser
    • 1
  • C. Schardt
    • 1
  • D. Brandscheidt
    • 2
  • E. Wollmer
    • 1
  • K. Havemann
    • 1
  1. 1.Abt. Haematologie/OnkologieZentrum Innere MedizinMarburgGermany
  2. 2.Thoraxklinik Heidelberg-RohrbachHeidelbergGermany

Personalised recommendations