Differential response to exercise in claudin-low breast cancer

Abstract

Exposure to exercise following a breast cancer diagnosis is associated with reductions in the risk of recurrence. However, it is not known whether breast cancers within the same molecular-intrinsic subtype respond differently to exercise. Syngeneic mouse models of claudin-low breast cancer (i.e., EO771, 4TO7, and C3(1)SV40Tag-p16-luc) were allocated to a uniform endurance exercise treatment dose (forced treadmill exercise) or sham-exercise (stationary treadmill). Compared to sham-controls, endurance exercise treatment differentially affected tumor growth rate: 1- slowed (EO771), 2- accelerated (C3(1)SV40Tag-p16-luc), or 3- was not affected (4TO7). Differential sensitivity of the three tumor lines to exercise was paralleled by effects on intratumoral Ki-67, Hif1-α, and metabolic programming. Inhibition of Hif1-α synthesis by the cardiac glycoside, digoxin, completely abrogated exercise-accelerated tumor growth in C3(1)SV40Tag-p16-luc. These results suggest that intratumoral Hif1-α expression is an important determinant of claudin-low breast cancer adaptation to exercise treatment.

Effect of post-implant exercise on tumour growth rate, perfusion and hypoxia in mice

“…1300-1500 mm 3 for non-exercising mice and 900 mm 3 for exercising mice) and only became apparent once tumours exceeded 600 mm 3 (i.e. there was no difference in growth rate up to a tumour size of 600 mm 3 [15,30]), which was the maximum ethical size used in our study. Thus, our study is consistent with previous data for EO771 tumours up to 600 mm 3 .…”

Efficacy of Exercise on Breast Cancer Outcomes: A Systematic Review and Meta-analysis of Preclinical Data

“…The negative results found in this variable were reported in five studies [9,21,46,66,73]. Each of them used a different tumor model that may have resulted in differences in tumor phenotypes and consequently in different behaviors when exposed to exercise [22,27,37]. However, no data were available regarding the different histological types of the developed tumors, and so we cannot know for sure whether this could be the case.…”

Exercício físico aeróbico de intensidade moderada reduz a velocidade de crescimento e modula o metabolismo energético tumoral em modelo experimental de câncer de mama triplo-negativo

“…Além disso, estima-se que o exercício aeróbico pode melhorar a perfusão e amenizar a hipoxia tumoral via estímulos angiogênicos e redução na expressão de HIF's em modelos xenográficos de câncer de mama (Betof et al, 2015;Khori et al, 2015;Isanejad et al, 2016;Wiggins et al, 2018). Contudo, a magnitude acerca do impacto do exercício físico no TME pode ser dependente do tipo tumoral (Glass et al, 2017).…”

“…Adicionalmente, a análise com três modelos experimentais classificados como TNBC do subtipo claudin-low, no qual os animais foram submetidos ao exercício aeróbico em esteira, exibiu diferentes sensibilidades ao treinamento (Glass et al, 2017). Neste estudo, os animais foram submetidos ao exercício aeróbico à 20 m/min, com 5% de inclinação por 45 min., cinco vezes por semana durante 15 dias.…”

“…Apesar do volume de células inoculadas serem 50% menor quando comparado ao grupo inoculado com EO771 células. Surpreendentemente, o grupo de animais transgênicos C3(1) SV40 Tag p16-luc, que desenvolvem espontaneamente o TNBC, apresentaram crescimento tumoral superior no grupo treinado (Glass et al, 2017).…”