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Journal of Cancer Research and Clinical Oncology

, Volume 117, Issue 6, pp 615–619 | Cite as

The role of insulin-related substance in Hodgkin's disease

  • T. Čabrijan
  • S. Levanat
  • B. Pekić
  • J. Pavelić
  • R. Spaventi
  • H. Frahm
  • V. Zjačič-Rotkvič
  • V. Goldoni
  • D. Vrbanec
  • M. Misjak
  • S. Grazio
  • K. Pavelić
Original Papers Clinical Oncology

Summary

An insulin-related growth-promoting substance was detected in the serum of a patient with Hodgkin's disease who suffered from severe hypoglycaemia, as well as in the supernatant of homogenized spleen tissue of the same patient. Low concentrations of this substance enhanced DNA synthesis of short-term-cultured spleen tumour cells obtained from the same patient, while the addition of anti-insulin antiserum interfered with that effect. Moreover, the preincubation of this insulin-related substance with the anti-insulin antiserum abrogated its stimulatory effect on tumour cell proliferation. Both insulin and the insulin-related substance bound to patients splenocytes to a similar extent. The data suggest that the insulin-related substance, found in this particular case of Hodgkin's disease, plays a role in tumour progression by an autocrine mechanism.

Key words

Insulin-related substance Hypoglycaemia Autocrine stimulation 

Abbreviations

SICRI

substance immunologically cross-reactive with insulin

PDGF

platelet-derived growth factor

EGF

epidermal growth factor

FGF

fibroblast growth factor

ECGF

endothelial cell growth factor

IGF

insulin-like growth factor

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References

  1. Bajzer Z, Pavelić K, Vuk-Pavlović S (1984) Growth self-incitement in murine melanoma B-16: a phenomenological model. Science 225:930–932Google Scholar
  2. Čabrijan T, Pačarizi H, Levanat S, Vrbanec D, Pavelić J, Milković D, Spaventi R, Končar M, Baltić V, Spaventi Š, Pavelić K (1988) Autocrine tumor growth regulation by the insulin growth factor I (IGF I) and the epidermal growth factor (EGF). In: Bresciani F et al. (eds) Progress in cancer research and therapy, vol 35. Hormones and Cancer 3. Raven, New York, pp 227–230Google Scholar
  3. Fraizier WA, Angeletti RH, Bradshaw AR (1972) Nerve growth factor and insulin. Structural similarities indicate an evolutionary relationship reflected by physiological action. Science 176:482–488Google Scholar
  4. Gammeltoft S, Gliemann J (1973) Binding and degradation of125I-labeled insulin by isolated non-fat cells. Biochim Biophys Acta 320:16–32Google Scholar
  5. Ginsberg BB, Kahn RC, Roth J, Megyesi K, Baumann G (1979) Identification and high yield purification of insulin-like growth factors (nonsuppressible insulin-like activities and somatomedins) from human plasma by use of endogenous binding proteins. J Clin Endocrinol Metab 48:42–49Google Scholar
  6. Hyvarinen A, Nikkila BY (1962) Specific determination of blood glucose witho-toluidine. Clin Chim Acta 7:140–143Google Scholar
  7. Levanat S, Pavelić K (1989) Isolation and purification of a substance immunologically cross-reactive with insulin (SICRI) from tumor tissue. Int J Biochem 21:509–515Google Scholar
  8. Levanat S, Pavelić K (1990) Isolation and purification of substance immunologically cross reactive with insulin from murine myeloid leukemia. Biol Chem Hoppe-Seyler 371:250–254Google Scholar
  9. Morgan CR, Lazarow (1963) Immunoassay of insulin. Two antibody systems. Plasma insulin levels of normal, subdiabetic and diabetic rats. Diabetes 12:115–121Google Scholar
  10. Pavelić K (1979) Aplastic carcinoma in diabetic mice: hyperglycemia suppresses proliferation rate and insulin synthesis by tumor cells. J Natl Cancer Inst 62:139–141Google Scholar
  11. Pavelić K, Popović M (1981) Insulin and glucagon secretion by renal adenocarcinoma. Cancer 48:98–100Google Scholar
  12. Pavelić K, Vuk-Pavlović S (1983) C-peptide does not parallel increase of serum levels of substances immunologically cross-reactive with insulin in non-Hodgkin's lymphoma patients. Blood 61:925–928Google Scholar
  13. Pavelić K, Pekić B, Slijepčević M, Popović M (1980) Insulin levels in Hodgkin's disease. Br J Haematol 46:133–135Google Scholar
  14. Pavelić K, Odavić M, Pekić B, Hršak I, Vuk-Pavlović S (1982a) Correlation of substance(s) immunologically cross-reactive with insulin, glucose and growth hormone in Hodgkin's lymphoma patients. Cancer Lett 17:81–86Google Scholar
  15. Pavelić K, Bolanča M, Veček N, Pavelić J, Marotti T, Vuk-Pavlović S (1982b) Carcinoma of the cervix and corpus uteri in humans: stage-dependent blood levels of substance(s) immunologically cross-reactive with insulin. J Natl Cancer Inst 68:891–894Google Scholar
  16. Pavelić K, Vrbanec D, Marušić S, Levanat S, Čabrijan T (1986) Autocrine growth regulation by somatomedin C: an in vitro model. J Endocrinol 109:233–238Google Scholar
  17. Pavelić LJ, Pavelić K, Vuk-Pavlović S (1984) Human mammary and bronchial carcinomas. In vivo and in vitro secretion of substances immunologically cross-reactive with insulin. Cancer 53:2467–2471Google Scholar
  18. Shields R (1977) Growth factors for tumors. Nature 267:308Google Scholar
  19. Sporn MB, Todaro GL (1980) Autocrine secretion and malignant transformation of cells. N Engl J Med 303:878–880Google Scholar
  20. Vuk-Pavlović S, Opara EC, Levanat S, Vrbanec D, Pavelić K (1986a) Autocrine tumor growth regulation and tumor associated hypoglycemia in murine melanoma B 16 in vivo. Cancer Res 46:2208–2213Google Scholar
  21. Vuk-Pavlović Z, Pavelić K, Vuk-Pavlović S (1986b) Modulation of in vitro growth of murine leukemia by an autologous substance immunochemically cross-reactive with insulin and antiinsulin serum. Blood 67:1031–1035Google Scholar
  22. Županović Ž, Gabrilovac J, Brayer D, Ročić B, Pavelić K (1983) Insulin receptors on cells of mouse myeloid leukemia. Period Biol 85:97–98Google Scholar

Copyright information

© Springer-Verlag 1991

Authors and Affiliations

  • T. Čabrijan
    • 1
  • S. Levanat
    • 2
  • B. Pekić
    • 2
  • J. Pavelić
    • 2
  • R. Spaventi
    • 2
  • H. Frahm
    • 3
  • V. Zjačič-Rotkvič
    • 1
  • V. Goldoni
    • 1
  • D. Vrbanec
    • 4
  • M. Misjak
    • 1
  • S. Grazio
    • 1
  • K. Pavelić
    • 2
  1. 1.University Hospital “Sestre milosrdnice”ZagrebCroatia
  2. 2.Ruder Bošković InstituteZagrebCroatia
  3. 3.University Hospital EppendorfHamburg 20Germany
  4. 4.University Hospital KBC RebroZagrebCroatia

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