Biphasic effect of a primary tumor on the growth of secondary tumor implants

Abstract

Background

The phenomenon of hormesis is characterized by a biphasic dose–response, exhibiting opposite effects in the low- and high-dose zones. In this study, we explored the possibility that the hormesis concept may describe the interactions between two tumors implanted in a single mouse, such that the resulting tumors are of different sizes.

Materials and methods

We used two murine tumors of spontaneous origin and undetectable immunogenicity growing in BALB/c mice. A measure of cell proliferation was obtained by immunostaining for Ki-67 protein and by using the [3H] thymidine uptake assay. For serum fractionation, we utilized dialysis and chromatography on Sephadex G-15.

Results

The larger primary tumor induced inhibitory or stimulatory effects on the growth of the smaller secondary one, depending on the ratio between the mass of the larger tumor relative to that of the smaller one, with high ratios rendering inhibition and low ratios inducing stimulation of the secondary tumor.

Conclusion

Since metastases can be considered as natural secondary tumor implants in a tumor-bearing host and that they constitute the main problem in cancer pathology, the use of the concept of hormesis to describe those biphasic effects might have significant clinical implications. In effect, if the tumor-bearing host were placed in the inhibitory window, tumor extirpation could enhance the growth of distant metastases and, reciprocally, if placed in the stimulatory window, tumor extirpation would result not only in a reduction or elimination of primary tumor load but also in a slower growth or inhibition of metastases.

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Acknowledgments

This work was supported by grants from CONICET (Consejo Nacional de Investigaciones Científicas y Técnicas), Fundación Roemmers and Agencia Nacional de Promoción Científica y Tecnológica (PICT 05-38197/2005), Argentina. The authors are grateful to Dr. Richmond T. Prehn and Dra. Christiane D. Pasqualini for critical discussion of this article.

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Correspondence to Raúl A. Ruggiero.

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Bruzzo, J., Chiarella, P., Meiss, R.P. et al. Biphasic effect of a primary tumor on the growth of secondary tumor implants. J Cancer Res Clin Oncol 136, 1605–1615 (2010). https://doi.org/10.1007/s00432-010-0818-7

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Keywords

  • Murine tumors
  • Hormesis
  • Biphasic dose–response
  • Secondary tumor implants
  • Metastases