Reprogramming energy metabolism and inducing angiogenesis: co-expression of monocarboxylate transporters with VEGF family members in cervical adenocarcinomas
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Data
2015
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Background: Deregulation of cellular energetic metabolism was recently pointed out as a hallmark of cancer cells.
This deregulation involves a metabolic reprogramming that leads to a high production of lactate. Lactate efflux,
besides contributing for the glycolytic flux, also acts in the extracellular matrix, contributing for cancer malignancy,
by, among other effects, induction of angiogenesis. However, studies on the interplay between cancer metabolism
and angiogenesis are scarce. Therefore, the aim of the present study was to evaluate the metabolic and vascular
molecular profiles of cervical adenocarcinomas, their co-expression, and their relation to the clinical and pathological
behavior.
Methods: The immunohistochemical expression of metabolism-related proteins (MCT1, MCT4, CD147, GLUT1 and
CAIX) as well as VEGF family members (VEGF-A, VEGF-C, VEGF-D, VEGFR-1, VEGFR-2 and VEGFR-3) was assessed in a
series of 232 cervical adenocarcinomas. The co-expression among proteins was assessed and the expression profiles
were associated with patients’ clinicopathological parameters.
Results: Among the metabolism-related proteins, MCT4 and CAIX were the most frequently expressed in cervical
adenocarcinomas while CD147 was the less frequently expressed protein. Overall, VEGF family members showed a
strong and extended expression with VEGF-C and VEGFR-2 as the most frequently expressed and VEGFR-1 as the less
expressed member. Co-expression of MCT isoforms with VEGF family members was demonstrated. Finally, MCT4 was
associated with parametrial invasion and HPV18 infection, CD147 and GLUT1 with distant metastasis, CAIX with tumor
size and HPV18 infection, and VEGFR-1 with local and lymphnode metastasis.
Conclusions: The results herein presented provide additional evidence for a crosstalk between deregulating cellular
energetics and inducing angiogenesis. Also, the metabolic remodeling and angiogenic switch are relevant to cancer
progression and aggressiveness in adenocarcinomas.
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Angiogenesis, VEGF, Cervical adenocarcinoma, Monocarboxylate transporter, HPV, Metabolic reprogramming, Hypoxia, Lymphangiogenesis
Citação
PINHEIRO, Céline et al. Reprogramming energy metabolism and inducing angiogenesis: co-expression of monocarboxylate transporters with VEGF family members in cervical adenocarcinomas. BMC Cancer, New York, v. 15, p. 1- 11, 2015.