Differential sensitivities to lactate transport inhibitors of breast cancer cell lines

• Type: Article in International Scientific Journal
• Date: 2014

Authors

Morais Santos, F (Author) Other; Miranda Goncalves, V (Author) Other; Pinheiro, S (Author) Other; Vieira, AF (Author) Other; Paredes, J (Author) Other; Fernando Schmitt (Author) FMUP; Baltazar, F (Author) Other; Pinheiro, C (Author) Other

Journal

Title: Endocrine-Related Cancer

Vol. 21

Pages: 27-38

ISSN: 1351-0088

Publisher: BioScientifica Ltd.

Indexing

ISI Web of Knowledge - 54 Citations

Scopus - 57 Citations

Other information

Authenticus ID: P-009-4HV

DOI: 10.1530/erc-13-0132

Abstract (EN): 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 a-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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 12