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. 2015 Nov 2:15:835.
doi: 10.1186/s12885-015-1842-4.

Reprogramming energy metabolism and inducing angiogenesis: co-expression of monocarboxylate transporters with VEGF family members in cervical adenocarcinomas

Céline Pinheiro  1   2   3   4 , Eduardo A Garcia  5   6 , Filipa Morais-Santos  7   8 , Marise A R Moreira  9 , Fábio M Almeida  10 , Luiz F Jubé  11 , Geraldo S Queiroz  12 , Élbio C Paula  13 , Maria A Andreoli  14   15 , Luisa L Villa  16   17   18 , Adhemar Longatto-Filho  19   20   21   22 , Fátima Baltazar  23   24
Affiliations

Reprogramming energy metabolism and inducing angiogenesis: co-expression of monocarboxylate transporters with VEGF family members in cervical adenocarcinomas

Céline Pinheiro et al. BMC Cancer. .

Abstract

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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Figures

Fig. 1
Fig. 1
Immunohistochemical expression of MCT1, MCT4, CD147, GLUT1 and CAIX in cervical adenocarcinoma samples. Expression of proteins was more frequently found in the plasma membrane of cells as shown in (a) for MCT1, (b) for MCT4, (c) for CD147, (d) for GLUT1 and (e) for CAIX. Nuclear expression was also observed in some cases for GLUT1 (F)
Fig. 2
Fig. 2
Immunohistochemical expression of VEGF family in cervical adenocarcinoma samples. (a) VEGF-A; (b) VEGF-C; (c) VEGF-D; (d) VEGFR-1; (e) VEGFR-2; and (f) VEGFR-3
See this image and copyright information in PMC

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