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BMC Cancer
Published in: BMC Cancer 1/2014

Open Access 01-12-2014 | Research article

Lactate transporters and vascular factors in HPV-induced squamous cell carcinoma of the uterine cervix

Authors: Céline Pinheiro, Eduardo A Garcia, Filipa Morais-Santos, Cristovam Scapulatempo-Neto, Allini Mafra, Renske DM Steenbergen, Enrique Boccardo, Luisa L Villa, Fátima Baltazar, Adhemar Longatto-Filho

Published in: BMC Cancer | Issue 1/2014

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Abstract

Background

Tumour microenvironment is a fundamental aspect of tumour behaviour, modulating important events as cancer cell migration and invasion, as well as angiogenesis and metastisation. Among other microenvironment features, hypoxia and acidity play important roles in this modulation. As the metabolic reprogramming of cancer cells induces extracellular acidity, which in turn induces angiogenesis, and hypoxia induces both the metabolic reprogramming and angiogenesis, the present study aims to evaluate the immunohistochemical expression of a variety of metabolic and vascular markers as common targets of the hypoxic microenvironment in a series of cervical squamous cells carcinoma, as well as using an in vitro 3D culture model.

Methods

Immunohistochemical expression of MCT1, MCT4, CD147, GLUT1 and CAIX was assessed in a series of 28 chronic cervicitis, 34 LSIL, 29 HSIL, 38 cases of squamous cells carcinoma (SCC), as well as in in vitro 3D culture of keratinocytes expressing HPV genes. Furthermore, VEGF family members’ expression was assessed in the SCC cases. The expression profiles were associated with patients’ clinicopathological parameters.

Results

We found an increase of MCT4 expression along progression to malignancy in cervical samples. Also, MCT4 was associated with CD147 and CAIX expression. VEGF-A expression was more frequently found in cases without MCT1 expression. Both MCT4 and CD147 were more frequently expressed in younger patients at diagnosis while no associations were found between VEGF family and clinicopathological parameters. Finally, we show evidence for the upregulation of MCT4, as well as CD147 and CAIX, after HPV transfection.

Conclusions

The results herein presented point at MCT4 as a promising therapeutic target in squamous cells carcinoma of the uterine cervix. Importantly, we show a possible association between lactate transport and angiogenesis, which should be further explored.
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Metadata
Title
Lactate transporters and vascular factors in HPV-induced squamous cell carcinoma of the uterine cervix
Authors
Céline Pinheiro
Eduardo A Garcia
Filipa Morais-Santos
Cristovam Scapulatempo-Neto
Allini Mafra
Renske DM Steenbergen
Enrique Boccardo
Luisa L Villa
Fátima Baltazar
Adhemar Longatto-Filho
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2014
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-14-751

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