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

JUAN BRUZZO; PAULA CHIARELLA; ROBERTO P. MEISS; RAÚL A. RUGGIERO

JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY

SPRINGER

Año: 2010 p. 1605 - 1615

0171-5216

The phenomenon of hormesis is characterized by a non-monotonic dose-response, that is biphasic, exhibiting stimulation in the low dose zone, followed by an inhibitory response at higher doses. Although over the past century the concept of hormesis became marginalized in the biomedical literature, the last years have witnessed growing evidence of hormetic dose responses occurring in many biological models. In this paper, we have explored the possibility that the hormesis concept may also describe the interactions between two tumors implanted in a single mouse, such that, either by the relative timing of the inoculations or by using different number of tumor cells per inoculum, the resulting tumors are of different sizes. In such cases we have found that 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. 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. For example, the definition of the windows of stimulation and inhibition in the relationship between the primary tumor and its metastases might help physicians to decide, in each particular case, the best therapeutic strategy, taking into account that if the tumor-bearing host were placed in the inhibitory window, tumor extirpation could enhance the growth of distant metastases and reciprocally, if it were 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.