Exercise oncology: the use of three-dimensional cell culture models for the translational research of cancer recurrence and dormancy.

Purpose: The use of cell culture models in exercise oncology has recently received growing interest [1]. Particularly, three-dimensional (3D) cell culture models are useful to translational research, mimicking the biological processes related to cancer recurrence and dormancy. We propose a double 3D cell culture approach to evaluate the effects of exercise-conditioned human serum (HS) in both single cell-derived microtumor formation and cancer cell spheroids. Methods: Exercise-conditioned sera were obtained from 12 healthy women before (t0) and immediately after (t1), after 4 h (t2), and 24 h (t3) of a high-intensity endurance cycling (HIEC) session. HIEC consisted of four 5-min stages at 50%, 55%, 60%, and 70% of individual maximal power (Pmax), which were followed by ten 90-s sprints at 90% Pmax separated by 180-s at 55% Pmax. Breast cancer (BC) cells were cultured in semisolid medium (soft agar) and U-shaped low attachment microplates to form microtumors and spheroids, respectively. Results: All of the HIEC-conditioned sera (t1, t2, and t3) markedly impacted the proliferative and the microtumor-forming capacity of BC cells in the semisolid medium, while the HS collected from the subjects at rest (t0) did not [2]. The microtumors-forming capacity of HIEC-conditioned HS was less than 30% compared to that induced by HS taken at rest. In addition, the BC spheroids were affected by post-HIEC human sera, showing a decrease in cell viability and spheroidization compared to spheroids cultured with HS taken at rest. Conclusions: These results demonstrated the potential of HIEC bouts in tumor progression control and tumor morphological changes, highlighting the importance of 3D models in advancing knowledge about the mechanisms through which exercise acts on cancer dormancy and recurrence. Moreover, the precise evaluation of the effects induced by exercise at different intensities could identify physiological predictors of cancer progression inhibition, ultimately improving our understanding of the relationship between physical exercise and cancer progression control, allowing us to optimize recommendations and exercise protocols for cancer recurrence prevention. References 1. Metcalfe RS, Kemp R et al. (2021) Anti-carcinogenic effects of exercise-conditioned human serum: evidence, relevance and opportunities. Eur J Appl Physiol 121(8):2107–2124. 2. Baldelli G, De Santi M et al. (2021) The effects of human sera conditioned by high-intensity exercise sessions and training on the tumorigenic potential of cancer cells. Clin Transl Oncol 23(1):22–34.