Abstract
The effects of both mechanical trauma and regeneration on the growth of intraportally injected tumor in the rat liver were investigated using two-thirds partial hepatectomy (PH). Tumor grew at the excision scar when PH was performed less than 2 days before tumor injection (34/34 animals). However, when the PH was performed 4–7 days before injection, tumor developed within the regenerating lobe, but not at the scar (50/51). Injecting the same cell dose into rats with intact livers caused few tumors to develop in 12/30 animals. Intraportally injected51Cr-labelled tumor cells distributed uniformly in the liver irrespective of the time after PH. Patterns of tumor take seen at different times after PH were not due to selective trapping of the injected cells. Liver extracts showed that epidermal growth factor-like activity was unaltered by PH, while heparin-binding growth factor activity peaked at 2 days post-PH, before the incidence of tumor growth in the parenchyma increased. We observed two peaks of DNA synthesis at days 1 and 4 post-PH by pulse labeling with [125I]deoxyuridine and bromodeoxyuridine. Bromodeoxyuridine immunohistochemistry showed the first peak to be confined to hepatocytes. The second peak involved non-hepatocytes and coincided with the beginning of enhanced tumor take in the regenerating lobe.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Alexander, J. W., andAltemeier, W. A., 1964, Susceptibility of injured tissues to haematogenous metastases: an experimental study.Annals of Surgery,159, 933–944.
Bouwens, L., Baekeland, M., andWisse, E., 1982, Importance of local proliferation in the expanding Kupffer cell population after zymosan stimulation and partial hepatectomy.Hepatology,4, 213–219.
Bouwens, L., Knook, D. L., andWisse, E., 1986, Local proliferation and extrahepatic recruitment of Kupffer cells in partial-body irradiated rats.Journal of Leukocyte Biology,39, 687–697.
Bucher, N. L. R., Patel, U., andCohen, S., 1977, Hormonal factors and liver growth.Advances in Enzyme Regulation, edited by G. Weber (New York: Pergamon), pp. 205–213.
Burki, K., Schaer, J. C., Gretillat, P., andSchindler, R., 1975, Radioactively labeled iododeoxyuridine in the experimental liver regeneration.Current Topics in Pathology,60, 33–61.
Fisher, B., andFisher, E. R., 1959, Experimental studies of factors influencing hepatic metastases: II. Effect of partial hepatectomy.Cancer,12, 929–932.
Fisher, B., andFisher, E. R., 1959, Experimental studies of factors influencing hepatic metastases: III. Effect of surgical trauma with special reference to liver injury.Annals of Surgery,150, 731–744.
Fisher, E. R., andFisher, B., 1960, Experimental studies of factors influencing hepatic metastases: IV. Effect of cirrhosis.Cancer,13, 860–864.
Fisher, E. R., andFisher, B., 1965, Experimental study of factors influencing development of hepatic metastases from circulating tumour cells.Acta Cytologica,9, 146–158.
Grisham, J. W., Leong, G. F., Albright, M. L., andEmerson, J. D., 1962, Effect of exchange transfusion on labeling of nuclei with3H-thymidine and on mitosis in hepatocytes of normal and regenerating rat liver.Cancer Research,26, 1476–1485.
Higgins, G. M., andAnderson, R. M., 1931, Experimental pathology of the liver.Archives of Pathology,12, 186–202.
Hoffman, B., andPaul, D., 1990, Basic fibroblast growth factor and transforming growth factor-alpha are hepatotrophic mitogensin vitro.Journal of Cellular Physiology,142, 149–154.
Hunt, T. K., Conolly, W. B., Aronson, S. B., andGoldstein, P., 1978, Anaerobic metabolism and wound healing: a hypothesis for the initiation and cessation of collagen synthesis in wounds.American Journal of Surgery,135, 328–332.
Ichihashi, H., Mabuchi, H., Suenaga, M., andKondo, T., 1984, Liver regeneration and tumour growth in the rat after partial hepatectomy.Japanese Journal of Surgery,14, 510–514.
Jones, F. S., andRous, P., 1914, On the cause of the localization of secondary tumours at point of injury.Journal of Experimental Medicine,20, 404–412.
Kann, M., Huang, J., Mansson, P. E., Yamamitsu, H., Carr, B., andMcKeehan, W. L., 1989, Heparin-binding growth factor type 1 (acidic fibroblast growth factor): A potential biphasic autocrine and paracrine regulator of hepatocyte regeneration,Proceedings of the National Academy of Science, U.S.A.,86, 7432–7436.
Knighton, D. R., Hunt, T. K., Thakral, K. K., andGoodson, W. H., 1982, Role of platelets and fibrin in the healing sequence. Anin vitro study of angiogenesis and collagen synthesis.Annals of Surgery,196, 379–387.
Leffert, H. L., Koch, K. S., Moran, T., andRubalcava, B., 1979, Hormonal control of rat liver regeneration,Gastroenterology,76, 1470–1482.
Leibovich, S. J., andRoss, R., 1974, The role of the macrophage in wound repair.American Journal of Pathology,78, 71–91.
Maguad, J. P., Sargent, I., Clarke, P. J., French, M., Rimock, R., andMason, D. Y., 1989, Double immunocytochemical labeling of cell and tissue samples with monoclonal antibromodeoxyuridine.Journal of Histochemistry and Cytochemistry,37, 1517–1527.
Mead, J. E., andFausto, N., 1988, Transforming growth factorα may be a physiological regulator of liver regeneration by means of an autocrine mechanism.Cell Biology,86, 1558–1562.
Murphy, P., Alexander, P., Kirkham, N., Fleming, J., andTaylor, I., 1986, Pattern of spread of bloodborne tumour.British Journal of Surgery,73, 829–834.
Murphy, P., Alexander, P., Senior, P. V., Fleming, J., Kirkham, N., andTaylor, I., 1988, Mechanism of organ selective tumour growth by bloodborne cancer cells.British Journal of Cancer,57, 19–31.
Rapolee, D. A., Mark, D., Banda, M. J., andWerb, Z., 1988, Wound macrophages express TGF-α and other growth factorsin vivo: Analysis by mRNA phenotyping.Science,241, 708–712.
Robinson, K. P., andHoppe, E., 1962, The development of bloodborne metastases. Effect of local trauma and ischaemia.Archives of Surgery,85, 720–724.
Skipper, D., Jeffrey, M. J., Cooper, A. J., Alexander, P., andTaylor, I., 1989, Enchanced growth of tumour cells in healing colonic anastomoses and laparatomy wounds.International Journal of Colorectal Disease,4, 172–177.
Strain, A. J., 1988, Transforming growth factorβ and inhibition of hepatocellular proliferation.Scandinavian Journal of Gastroenterology,23 (Suppl.), 37–45.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Loizidou, M.C., Lawrance, R.J., Holt, S. et al. Facilitation by partial hepatectomy of tumor growth within the rat liver following intraportal injection of syngeneic tumor cells. Clin Exp Metast 9, 335–349 (1991). https://doi.org/10.1007/BF01769354
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01769354