Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Influence of dispase and angiogenesis factors on the growth of human xenografts

Summary

The growth development of a human adenocarcinoma, derived from the sigmoid colon and heterotransplanted to athymic, nude mice, was observed after pretreatment of the assigned site of transplantation (a) with the neutral protease dispase, (b) with angiogenic factors, such as prostaglandin E1 (PGE1) and phorbol 12-myristate 13-acetate (PMA), (c) with endothelial cell growth factor, or (d) with homogenized tumor material. The substances or preparations were applied several times within 1, 2, 3, or 4 days before tumor transplantation to nude mice. Following pretreatment with dispase or PGE1, tumor development was accelerated as a function of the doses and regimens applied, whereby the initial events after tumor transplantation, consisting of the removal of necrotic tumor cells and the invasion of host-supplied connective tissue into the xenografts, were obviously accelerated, resulting in an earlier beginning of exponential tumor growth. On days 25 and 28, the volumes of tumors pretreated with dispase or PGE1 exceeded those of control tumors by factors of between 3 and 5. Whereas applications of the phorbol ester PMA or endothelial growth factor did not influence tumor development, pretreatment with homogenized tumor material also effected acceleration of tumor development by about 7 days and increases of the final tumor volume by factors of between 2 and 3. These results underline the stimulating function of host-supplied connective tissue for the development of xenografted human tumors and open new perspectives to influence the growth velocity and, possibly, also the take-rates of human tumors in nude mice.

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

References

  1. Auerbach R (1981) Angiogenesis-inducing factors: a review. Lymphokines 4:69–88

  2. Barkla DH, Tutton PJM (1983) Temporal morphologic changes in human colorectal carcinomas following xenografting. Am J Pathol 110:315–321

  3. Bastert GB, Fortmeyer HP, Schmidt-Matthiesen H (1981) Thymusaplastic nude mice and rats in clinical oncology. Fischer, Stuttgart New York

  4. Bennet A (1982) Effect of prostaglandin synthesis inhibitors on tumor growth in vivo: In: Prostaglandins and cancer, First International Conference, Liss, New York, pp 759–766

  5. Fiebig HH, Schuchardt C, Henss H, Fiedler L, Löhr GW (1984) Comparison of tumor response in nude mice and in the patients. Behring Inst Mitt 74:343–352

  6. Folkman J (1985) Tumor angiogenesis. Adv Cancer Res 43:175–203

  7. Giraldi T, Perissin L, Zorzet S, Decorti G, Steven FS (1985) Tumor cell metastasis and surface neutral proteinase: effects of antimetastatic and antitumor drugs. Invasion Metastasis 5:336–343

  8. Gross JL, Moscatelli D, Jaffe EA, Rifkin DB (1982) Plasminogen activator and collagenase production by cultured capillary endothelial cells. J Cell Biol 95:974–981

  9. Houchens DP, Ovejera AA, Barker AD (1978) The therapy of human tumors in athymic (nude) mice. In: Houchens DP, Ovejera AA (eds) The use of athymic (nude) mice in cancer research. Fischer. Stuttgart New York, pp 267–280

  10. Köpf-Mater P (1986) Dying and regeneration of human tumor cells after heterotransplantation to athymic mice. Histol Histopathol 1:383–390

  11. Köpf-Maier P, Jäckel M (1989) Proliferation behavior of xenografted human tumors: a flow cytometric study. Anticancer Res (in press)

  12. Montesano R, Orci L (1985) Tumor-promoting phorbol esters induce angiogenesis in vitro. Cell 42:469–477

  13. Povlsen CO, Rygaard J (1971) Heterotransplantation of human adenocarcinomas of the colon and rectum to the mouse mutant nude. A study of nine consecutive transplantations. Acta Pathol Microbiol Scand [A] 79:159–169

  14. Schor AM, Schor SL (1983) Tumor angiogenesis. J Pathol 141:385–413

Download references

Author information

Correspondence to P. Köpf-Maier.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Köpf-Maier, P., Kestenbach, U. Influence of dispase and angiogenesis factors on the growth of human xenografts. J Cancer Res Clin Oncol 114, 547–552 (1988). https://doi.org/10.1007/BF00398175

Download citation

Key words

  • Dispase
  • Angiogenesis factors
  • Human heterotransplanted colon carcinoma
  • Growth enhancement