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


OBJECTIVE
This work aimed to evaluate the effects of long-term exercise training on the growth and vascularization of mammary tumors in a rat model.


METHODS
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).


RESULTS
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.


CONCLUSIONS
Long-term exercise training increased VEGF-A expression, leading to enhanced tumor vascularization and reduced tumor burden, multiplicity and histological aggressiveness.
Department of Veterinary Sciences, School of Agrarian and Veterinary Sciences, University of Trás-os-Montes and Alto Douro (UTAD), Vila Real, Portugal; Center for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), UTAD, Vila Real, Portugal; Animal and Veterinary Research Center (CECAV), UTAD, Vila Real, Portugal; Organic Chemistry, Natural Products and Foodstuffs (QOPNA), Mass Spectrometry Center, Department of Chemistry, University of Aveiro, Aveiro, Portugal. Electronic address: anafaustino.faustino@sapo.pt.
A I
AI
Faustino-Rocha
Institute of Science and Innovation in Mechanical and Industrial Engineering (INEGI), Faculty of Engineering (FEUP), University of Porto, Porto, Portugal.
A
A
Silva
Institute of Science and Innovation in Mechanical and Industrial Engineering (INEGI), Faculty of Engineering (FEUP), University of Porto, Porto, Portugal.
J
J
Gabriel
Laboratory for Process Environment Biotechnology and Energy Engineering (LEPABE), FEUP, University of Porto, Porto, Portugal; Molecular Oncology and Viral Pathology Group, CI-IPOP, Portuguese Institute of Oncology, Porto, Portugal.
R M
RM
Gil da Costa
Department of Veterinary Sciences, School of Agrarian and Veterinary Sciences, University of Trás-os-Montes and Alto Douro (UTAD), Vila Real, Portugal.
M
M
Moutinho
Department of Veterinary Sciences, School of Agrarian and Veterinary Sciences, University of Trás-os-Montes and Alto Douro (UTAD), Vila Real, Portugal; Center for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), UTAD, Vila Real, Portugal.
P A
PA
Oliveira
Department of Veterinary Sciences, School of Agrarian and Veterinary Sciences, University of Trás-os-Montes and Alto Douro (UTAD), Vila Real, Portugal; Animal and Veterinary Research Center (CECAV), UTAD, Vila Real, Portugal.
A
A
Gama
Organic Chemistry, Natural Products and Foodstuffs (QOPNA), Mass Spectrometry Center, Department of Chemistry, University of Aveiro, Aveiro, Portugal.
R
R
Ferreira
Department of Veterinary Sciences, School of Agrarian and Veterinary Sciences, University of Trás-os-Montes and Alto Douro (UTAD), Vila Real, Portugal; Center for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), UTAD, Vila Real, Portugal.
M
M
Ginja
D000818:Animals; D005260:Female; D007150:Immunohistochemistry; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply* / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D009929:Organ Size; D010805:Physical Conditioning, Animal; D017207:Rats, Sprague-Dawley; D013817:Thermography; D013997:Time Factors; D014463:Ultrasonography; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D042461:Vascular Endothelial Growth Factor A
Histopathology; MNU; Mammary tumors; Rat; Thermography; Ultrasonography; Vascularization