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Interlocking triads of growth control in tumors

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Abstract

A pair of growth control triads are used to describe coincident tumor growth and liver regeneration after partial hepatectomy. The models are extensions of previous growth control models which describe tumor growth in an unperturbed host (Michelson and Leith, 1991,Bull. math. Biol. 53, 639–656; idem, 1992, Proceedings of the Third International Conference on Communications and Control, Vol. 2, pp. 481–490; idem, 1992,Bull. math. Biol. 55, 993–1011; idem,J. theor. Biol. 169, 327–338). The linkage between the two triads depends upon systemic signals carried by soluble factors, and mathematical descriptors based upon biological first principals are proposed. The sources of the growth factors, their targets and the processing of their signals are investigated. Analyses of equilibrium in the constant coefficients case and simulated growth curves for the dynamic system are presented, and the effects of growth factor-induced mitogenesis and angiogenesis are discussed in particular. A case is made for early and late responses in the coupled control system. The biology of the signal processing paradigm is placed within a new theoretical context and discussed with regard to tumor adaptation, liver differentiation and the development of a tumor hypoxic fraction.

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Literature

  • Ankrapp, D. A. and D. B. Bevan. Insulin-like growth factor-1 and human lung fibroblast-derived insulin-like growth factor-1 stimulate the proliferation of human lung carcinoma cellin vitro. Cancer Res. 53, 3399–3404.

  • Asaga, T., K. Suzuki, M. Umeda, Y. Sugimasa, S. Takemiya and T. Okamoto. 1991. The enhancement of tumor growth after partial hepatectomy and the effect of sera obtained from hepatectomized rats on tumor cell growth.Japanese J. Surg. 21, 669–675.

    Article  Google Scholar 

  • Boutin, E. L., R. D. Sanderson, M. Bernfield and G. R. Cunha., 1991. Epithelial-mesenchymal interactions in the uterus and vagina alter the expression of the cell surface proteoglycan, syndecan.Dev. Biol. 148, 63–74.

    Article  Google Scholar 

  • Braun, L., J. E. Mead, M. Panzica, R. Mikumo, G. I. Bell and N. Fausto. 1988. Transforming growth factor beta mRNA increases during liver regeneration: a possible paracrine mechanism of growth regulation.Proc. natn Acad. Sci. U.S.A. 85, 1539–1543.

    Article  Google Scholar 

  • Cunha, G. R., P. Young, S. J. Higgins and P. S. Cooke. 1991. Neonatal seminal vesicle mesenchyme induces a new morphological and functional phenotype in the epithelia of adult ureter and ductus deferens.Development.111, 145–158.

    Google Scholar 

  • Donjacour, A. A. and G. R. Cunha. 1991. Stromal regulation of epithelial function.Cancer Treat. and Res. 53, 335–364.

    Google Scholar 

  • Durrant, L. G., S. A. Watson, A. Hall and D. L. Morris. 1991. Co-stimulation of gastrointestinal tumor cell growth by gastrin, transforming growth factor-α and insulin-like growth factor-1.Br. J. Cancer 63, 67–70.

    Google Scholar 

  • Fausto, N. 1991. Growth factors in liver development, regeneration, and carcinogenesis.Progr. Growth Factor Res. 3, 219–234.

    Article  Google Scholar 

  • Fidler, I. J. 1991. Orthotopic implantation of human colon carcinoma into nude mice provides a valuable model for the biology and therapy of metastasis.Cancer and Metastat. Rev. 10, 229–243.

    Article  Google Scholar 

  • Fisher, B. and E. R. Fisher. 1959a. Experimental studies of factors influencing hepatic metastases I. The effect of the number of tumor cells injected and the time of growth.Cancer 12, 926–928.

    Article  Google Scholar 

  • Fisher, B. and E. R. Fisher. 1959b. Experimental studies of factors influencing hepatic metastases II. Effect of partial hepatectomy.Cancer 12, 929–932.

    Article  Google Scholar 

  • Fisher, B. and E. R. Fisher. 1959c. Experimental studies of factors influencing hepatic metastases III. Effect of surgical trauma with special reference to liver injury.Ann. Surg. 150, 731–744.

    Google Scholar 

  • Fujiwara, K., S. Nagoshi, A. Ohno, K. Hirata, Y. Ohta, S. Mochida, T. Tomiya, K. Higashio and K. Kurokawa. 1993. Stimulation of liver growth by exogenous human hepatocyte growth factor in normal and partial hepatecomized rats.Hepatology 18, 1443–1449.

    Article  Google Scholar 

  • Gahary, A., G. Y. Minuk, J. Lao, T. Gauthier and L. J. Murphy. 1992. Effects of partial hepatectomy on hepatic insulin-like growth factor binding protein-1 expression.Hepatology 15, 1125–1131.

    Google Scholar 

  • Hayashi, N. and G. R. Cunha. 1991. Mesenchyme-induced changes in the neoplastic characteristics of the Dunning prostatic adenocarcinoma.Cancer Res. 51, 4924–4930.

    Google Scholar 

  • Hayashi, N., G. R. Cunha and Y. C. Wong. 1990. Influence of male genital tract mesenchymes on the differentiation of dunning prostatic adenocarcinoma.Cancer Res. 50, 4747–4754.

    Google Scholar 

  • Kan, M., J. Huan, P. Mansson, H. Yamsumitsu, B. Carr and W. McKeehan. 1989 Heparin-binding growth factor type II (acidic fibroblast growth factor): a potential biphasic autocrine and paracrine regulator of hepatocyte regeneration.Proc. natn. Acad. Sci. U.S.A. 86, 7432–7436.

    Article  Google Scholar 

  • Leith, J. T., P. Harrigan, G. Padfield and S. Michelson. 1991. Modification of growth rates and hypoxic fractions of xenografted A431 tumors by sialoadenectomy or exogenously supplied epidermal growth factor.Cancer Res. 51, 4111–4113.

    Google Scholar 

  • Leith, J. T., G. Padfield and S. Michelson. 1992. Effects of partial hepatectomy on the growth characteristics and hypoxic fractions of xenografted DLD-2 human colon cancers.Rad. Res. 132, 263–268.

    Google Scholar 

  • Loizidou, M. C., R. J. Lawerence, S. Holt, N. J. Carty, A. J. Cooper, P. Alexander and I. Taylor. 1991. Facilitation by partial hepatectomy of tumor growth within the rat liver following intraportal injection of syngeneic tumor cells.Clin. and Expl. Metastasis 9, 335–349.

    Article  Google Scholar 

  • Matsumoto, K. and T. Nakamura. 1992. Hepatocyte growth factor: molecular structure, roles in liver regeneration, and other biological factors.Crit. Rev. in Oncogenesis.3, 27–54.

    Google Scholar 

  • Mead, J. E. and N. Fausto. 1989. Transforming growth factor alpha may be a physiological regulator of liver regeneration by means of an autocrine mechanism.Proc. nat. Acad. Sci. U.S.A. 86, 1558–1562.

    Article  Google Scholar 

  • Michelson, S. and J. T. Leith. 1991. Autocrine and paracrine growth factors in tumor growth.Bull. math. Biol. 53, 639–656.

    Google Scholar 

  • Michelson, S. and J. T. Leith. 1992a. The autocrine-paracrine-endocrine triad of tumor growth control. Proceedings of The Third International Conference on Communications and Control, Victoria, B.C., Oct. 16–18, 1991, Vol. 2, pp. 481–490.

  • Michelson, S. and J. T. Leith. 1992b Growth factors and growth control of heterogeneous cell populations.Bull. math. Biol. 55, 993–1011.

    Article  Google Scholar 

  • Michelson, S. and J. T. Leith. 1994. Dormancy, regression, and recurrence: towards a unifying theory of tumor growth control.J. theor. Biol. 169, 327–338.

    Article  Google Scholar 

  • Mohn, K. L., A. E. Melby, D. S. Tewari, T. M. Laz and R. Taub. 1991. The gene encoding rat insulin-like growth factor binding protein-1 is rapidly and highly increased in regenerating liver.Molec. cell Biol 11, 1393–1401.

    Google Scholar 

  • Namieno, T., N. Takeichi, Y. Hata, J. Uchinao and H. Kobayashi 1991. Kinetic changes of liver regeneration and hepatocellular carcinoma cells after partial hepatectomy in rats.Gastroenterologia Japonica 26, 29–36.

    Google Scholar 

  • Paschkis, K. E., A. Cantarow, J. Stasney and J. H. Hobbs. 1955 Tumor growth in partially hepatectomized rats.Cancer Res. 15, 579–582.

    Google Scholar 

  • Rockwell, S. and J. E. Moulder. 1990. Hypoxic fractions of human tumors xenografted into mice: a review.Int. J. Rad. Oncol. Biol. Phys. 19, 197–202.

    Google Scholar 

  • Rubin, J. S., A. M. Chan, D. P. Bottaro, W. H. Burgess, W. G. Taylor, A. C. Cech, D. W. Hirschfeld, J. Wong, T. Miki, P. W. Finch and S. A. Aeronson 1991. A broad-spectrum human lung fibroblast-derived mitogen is a variant of hepatocyte growth factor.Proc. natn. Acad. Sci. U.S.A. 88, 415–419.

    Article  Google Scholar 

  • Wong, Y. C., G. R. Cunha and N. Hayashi. 1992. Effects of mesenchyme of the embryonic urogenital sinus and neonatal seminal vesicle on the cytodifferentiation of the Dunning tumor: ultrastructural study.Acta Anatomica 143, 139–150.

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Biomathematics, Syntex Drug Discovery Research, 3401 Hillview Avenue, M/S S3-1B, 94303, Palo Alto, CA, U.S.A.

    Seth Michelson

  2. Department of Radiation Medicine, Radiation Research Laboratories, Brown University, Box G-B004, 02912, Providence, RI, U.S.A.

    John T. Leith

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Michelson, S., Leith, J.T. Interlocking triads of growth control in tumors. Bltn Mathcal Biology 57, 345–366 (1995). https://doi.org/10.1007/BF02460621

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  • DOI: https://doi.org/10.1007/BF02460621

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