Skip to main content
Log in

Cytokines may influence tumor growth and spread

An in vitro study in two human cancer cell lines

  • Original
  • Published:
International Journal of Clinical and Laboratory Research

Abstract

Tumor spread may be favored by a reduced production and/or an enhanced degradation of extracellular matrix components (collagen, fibronectin, laminin). Most tumor cell behavior, from growth to spread, may be regulated by cytokines, the exact roles of which, however, are not yet fully understood. We here evaluate the effects of some cytokines (epidermal growth factor, transforming growth factor-β1, interleukin-1α, and interleukin-1β) on both cell growth and the production of the aminoterminal peptide of type III procollagen, the urokinase plasminogen activator, and the plasminogen activator inhibitor-1 in neoplastic cell lines originating in the pancreas and colon. Cells were stimulated daily with the above cytokines and the aminoterminal peptide of type III procollagen, urokinase plasminogen activator, and plasminogen activator inhibitor-1 were measured in the conditioned media. Epidermal growth factor stimulated cell growth of both cell lines. Transforming growth factor-β1 counteracted cell proliferation and stimulated type III procollagen and plasminogen activator inhibitor-1 production only in the colon cancer cell line. Interleukin-1α slightly stimulated cell growth, but inhibited plasminogen activator inhibitor-1 production in both cell lines; interleukin-1 β did not affect cell growth, but stimulated plasminogen activator inhibitor-1 production by the colon cancer cell line. Our findings suggest that transforming growth factor-β1 and interleukin-1β may have an antidiffusive effect. These results confirm that cytokine-producing cells have a potential role in stimulating or counteracting tumor growth and spread and also confirm the pivotal role of host-tumor interactions in determining the outcome of a particular neoplasia.

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. Hart IR, Saini A. Biology of tumour metastasis. Lancet 1992; 339:1453.

    Article  PubMed  CAS  Google Scholar 

  2. Aznavoorian S, Murphy AN, Stetler-Stevenson G, Liotta LA. Molecular aspects of tumor cell invasion and metastasis. Cancer 1993;71:1368.

    Article  PubMed  CAS  Google Scholar 

  3. Van Roy F, Mareel M. Tumor invasion: effects of cell adhesion and motility. Trends Cell Biol 1992;2:163.

    Article  PubMed  Google Scholar 

  4. Jiang WG, Puntis MCA, Hallett MB. Molecular and cellular basis of cancer invasion and metastasis: implications for treatment. Br J Surg 1994;81:1576.

    Article  PubMed  CAS  Google Scholar 

  5. Zetter BR. The cellular basis of site-specific tumor metastasis. N Engl J Med 1990;322:605.

    Article  PubMed  CAS  Google Scholar 

  6. Liotta LA, Stetler-Stevenson WG. Tumor invasion and metastasis: an imbalance of positive and negative regulation. Cancer Res 1991;51:5054s.

    Google Scholar 

  7. Dano K, Andreason PA, Grondahl-Hansen J, Kristensen P, Nielsen LS, Skriver L. Plasminogen activators, tissue degradation and cancer. Adv Cancer Res 1985;44:139.

    PubMed  CAS  Google Scholar 

  8. Liu G, Shuman A, Cohen RL. Co-expression of urokinase, urokinase receptor and PAI-1 is necessary for optimum invasiveness of cultured lung cancer cells. Int J Cancer 1995;60:501.

    Article  PubMed  CAS  Google Scholar 

  9. Damjanovich L, Turzò C, Adany R. Factors involved in the plasminogen activation system in human breast tumours. Thromb Haemost 1994;71:684.

    PubMed  CAS  Google Scholar 

  10. Bianchi E, Cohen RL, Dai A, Thor AT, Shuman MA, Smith HS. Immunohistochemical localization of the plasminogen activator inhibitor-1 in breast cancer. Int J Cancer 1995;60:597.

    Article  PubMed  CAS  Google Scholar 

  11. Noguchi-Takino M, Endo Y, Yonemura Y, Sasaki T. Relationship between expression of plasminogen activator system and metastatic ability in human cancers. Int J Oncol 1996;8:97.

    Google Scholar 

  12. Bleady R, Tzanakis GN, Schwalke MA, Wanebo H, Vezeridis MP. Epidermal growth factor stimulation and metastatic rate in human pancreatic carcinoma cell lines. J Surg Res 1990;49:276.

    Article  Google Scholar 

  13. Barton CM, Hall PA, Hughes CM, Gullick WJ, Lemoine NR. Transforming growth factor alpha and epidermal growth factor in human pancreatic cancer. J Pathol 1991;163:111.

    Article  PubMed  CAS  Google Scholar 

  14. Baldwin RL, Korc M. Growth inhibition of human pancreatic carcinoma cells by transforming growth factor beta-1. Growth Factors 1993;8:23.

    Article  PubMed  CAS  Google Scholar 

  15. Rodeck U, Bossler A, Graeven U, Fox FE, Novell PC, Knabbe C, Kari C. Transforming growth factor B production and responsiveness in normal human melanocytes and melanoma cells. Cancer Res 1994;54:575.

    PubMed  CAS  Google Scholar 

  16. Holting T, Zileke A, Siperstein AE, Clark OH, Duh Q. Transforming growth factor-B1 is a negative regulator for differential thyroid cancer: studies of growth, migration, invasion, and adhesion of cultured follicular and papillary thyroid cancer cell lines. J Clin Endocrinol Metab 1994;79:806.

    Article  PubMed  CAS  Google Scholar 

  17. Walker RA, Dearing SJ, Gallacher B. Relationship of transforming growth factor B1 to extracellular matrix and stromal infiltrates in invasive breast carcinoma. Br J Cancer 1994;69:1160.

    PubMed  CAS  Google Scholar 

  18. Dinarello CA. The biological properties of interleukin-1. Eur Cytokine Netw 1994;5:517.

    PubMed  CAS  Google Scholar 

  19. Boraschi D, Villa L, Volpini G, Bossù P, Censini S, Ghiara P, Scapigliat G, Nencioni L, Baratalini, M, Matteucci G, Cioli F, Carnasciali M, Olmastroni E, Mengozzi M, Ghezzi P, Tagliabue A. Differential activity of interleukin 1 A and interleukin 1 B in the stimulation of the immune response in vivo. Eur J Immunol 1990:20:317.

    Article  PubMed  CAS  Google Scholar 

  20. Ebina T, Ishikawa L. Antitumor effect of interleukin-1 beta in the double grafted tumor system. Jpn J Cancer Res 1989;80:570.

    PubMed  CAS  Google Scholar 

  21. Dejana E, Bertocchi F, Bortolami MC, Regonesi, C, Tonta A, Breviario F, Giavazzi R. Interleukin 1 promotes tumor cell adhesion to cultured human endothelial cells. J Clin Invest 1988;82:1466.

    Article  PubMed  CAS  Google Scholar 

  22. Giavazzi R, Garofalo A, Bani MR, Abbate M, Ghezzi P, Boraschi D, Mantovani A, Dejana E. Interleukin 1-induced augmentation of experimental metastases from a human melanoma in nude mice. Cancer Res 1990;50:4771.

    PubMed  CAS  Google Scholar 

  23. Burrows FJ, Haskard DO, Hart IR, Marshall JF, Selkirk S, Poole S, Thorpe PE. Influence of tumor-derived interleukin 1 on melanoma-endothelial cell interactions in vitro. Cancer Res 1991;51: 4768.

    PubMed  CAS  Google Scholar 

  24. Chirivi RGS, Garofalo A, Martin Padura I, Mantovani A, Giavazzi R. Interleukin 1 receptor antagonist inhibits the augmentation of metastasis induced by interleukin 1 or lipopolysaccharide in a human melanoma/nude mouse system. Cancer Res 1993;53:5051.

    PubMed  CAS  Google Scholar 

  25. Vidal-Vanaclocha F, Amezaga C, Asumendi A, Kaplanski G, Dinarello CA. Interleukin-1 receptor blockade reduces the number and size of murine B16 melanoma hepatic metastases. Cancer Res 1994;54:2667.

    PubMed  CAS  Google Scholar 

  26. Yunis AA, Arimura GK, Russin DJ. Human pancreatic carcinoma (MIA PaCa-2) in continuous culture: sensitivity to asparaginase. Int J Cancer 1977;19:128.

    Article  PubMed  CAS  Google Scholar 

  27. Zupi G, Marangolo M, Arancia G, Greco C, Laudonio N, Iosi F, Formisano G, Malorni W. Modulation of the cytotoxic effect of 5-fluorouracil byN-methylformamide on a human colon carcinoma cell line. Cancer Res 1988;48:6193.

    PubMed  CAS  Google Scholar 

  28. Cohen MC, Cohen S. Cytokine function. A study in biological diversity. Am J Clin Pathol 1996;105:589.

    PubMed  CAS  Google Scholar 

  29. Opdenakker G, Van Damme J. Cytokines and proteases in invasive processes: molecular similarities between inflammation and cancer. Cytokine 1992;4:251.

    Article  PubMed  CAS  Google Scholar 

  30. Enayati P, Brennan MF, Fong Y. Systemic and liver cytokine activation. Arch Surg 1994;129:1159.

    PubMed  CAS  Google Scholar 

  31. Joh T, Itoh M, Yashue N, Niyamoto T, Iwai A, Matsusako K, Endoh K, Takeuchi T, Moriyama A, Kato T, Tanaka R. A sensitive immunoassay system of rat epidermal growth factor in biological fluids and tissue extracts. Acta Endocrinol (Copenh) 1989;120:616.

    CAS  Google Scholar 

  32. Tsushima H, Kawata S, Tamura S, Ito N, Shirai Y, Kiso S, Imai Y, Shimomukai H, Nomura Y, Matsuda Y, Matsuzawa Y. High levels of transforming growth factor B1 in patients with colorectal cancer: association with disease progression. Gastroenterology 1996;110:375.

    Article  PubMed  CAS  Google Scholar 

  33. Friess H, Yamanaka Y, Buchler M, Ebert M, Beger HG, Glod LI, Korc M. Enhancement expression of transforming growth factor B isoforms in pancreatic cancer correlates with decreased survival. Gastroenterology 1993;105:1846.

    PubMed  CAS  Google Scholar 

  34. Ito N, Kawata S, Tamura S, Shirai Y, Kiso S, Tsushima H, Matsuzawa Y. Positive correlation of plasma transforming growth factor-beta 1 levels with tumor vascularity in hepatocellular carcinoma. Cancer Lett 1995;89:45.

    PubMed  CAS  Google Scholar 

  35. Fischer JR, Darjes H, Lahm H, Schindel M, Drings P, Krammer PH. Constitutive secretion of bioactive transforming growth factor beta 1 by small cell lung cancer cell lines. Eur J Cancer 1994; 30A:2125.

    Article  PubMed  CAS  Google Scholar 

  36. Basso D, Plebani M, Fogar P, Panozzo MP, Meggiato T, De Paoli M, Del Favero G. Insulin-like growth factor-I. interleukin-1 A and B in pancreatic cancer: role in tumor invasiveness and associated diabetes. Int J Clin Lab Res 1995;25:40.

    Article  PubMed  CAS  Google Scholar 

  37. Fratelli M, Gagliardini V, Galli G, Gnocchi P, Ghiara P, Ghezzi P. Autocrine interleukin-1 beta regulates both proliferation and apoptosis in EL-4-6.1 thymoma cells. Blood 1995;85:3532.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Panozzo, M.P., Basso, D., De Paoli, M. et al. Cytokines may influence tumor growth and spread. Int J Clin Lab Res 26, 240–244 (1996). https://doi.org/10.1007/BF02602956

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02602956

Key words

Navigation