Long-term exercise training as a modulator of mammary cancer vascularization.

Abstract

Breast cancer remains a leading cause of death by cancer worldwide. It is commonly accepted that angiogenesis and the expression of angiogenic factors such as vascular endothelial growth factor-A (VEGF-A) is associated with the increased risk of metastasis and poor patient outcome. This work aimed to evaluate the effects of long-term exercise training on the growth and vascularization of mammary tumors in a rat model. Fifty female Sprague-Dawley rats were divided into four groups: two N-methyl-N-nitrosourea (MNU)-exposed groups (exercised and sedentary) and two control groups (exercised and sedentary). MNU was administered once, intraperitoneally at 7 weeks-old. Animals were then exercised on a treadmill for 35 weeks. Mammary tumors were evaluated using thermography, ultrasonography [Power Doppler (PDI), B Flow and contrast-enhanced ultrasound (CEUS)], and immunohistochemistry (VEGF-A). Both, MNU sedentary and exercised groups showed 100% of tumor incidence, but exercised animals showed less tumors with an increased latency period. Exercise training also enhanced VEGF-A immunoexpression and vascularization (microvessel density, MVD) (p<0.05), and reduced histological aggressiveness. Ultrasound and thermal imaging analysis confirmed the enhanced vascularization of tumors on exercised animals. Long-term exercise training increased VEGF-A expression, leading to enhanced tumor vascularization and reduced tumor burden, multiplicity and histological aggressiveness.