Differential sensitivities to lactate transport inhibitors of breast cancer cell lines.

Abstract:

:The tumour microenvironment is known to be acidic due to high glycolytic rates of tumour cells. Monocarboxylate transporters (MCTs) play a role in extracellular acidification, which is widely known to be involved in tumour progression. Recently, we have described the upregulation of MCT1 in breast carcinomas and its association with poor prognostic variables. Thus, we aimed to evaluate the effect of lactate transport inhibition in human breast cancer cell lines. The effects of α-cyano-4-hydroxycinnamate, quercetin and lonidamine on cell viability, metabolism, proliferation, apoptosis, migration and invasion were assessed in a panel of different breast cancer cell lines. MCT1, MCT4 and CD147 were differently expressed among the breast cancer cell lines and, as expected, different sensitivities were observed for the three inhibitors. Interestingly, in the most sensitive cell lines, lactate transport inhibition induced a decrease in cell proliferation, migration and invasion, as well as an increase in cell death. Results were validated by silencing MCT1 expression using siRNA. The results obtained here support targeting of lactate transport as a strategy to treat breast cancer, with a special emphasis on the basal-like subtype, which so far does not have a specific molecular therapy.

journal_name

Endocr Relat Cancer

journal_title

Endocrine-related cancer

authors

Morais-Santos F,Miranda-Gonçalves V,Pinheiro S,Vieira AF,Paredes J,Schmitt FC,Baltazar F,Pinheiro C

doi

10.1530/ERC-13-0132

subject

Has Abstract

pub_date

2013-12-16 00:00:00

pages

27-38

issue

1

eissn

1351-0088

issn

1479-6821

pii

ERC-13-0132

journal_volume

21

pub_type

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