title: 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.
authors.affiliation: School of Health Sciences, Life and Health Sciences Research Institute (ICVS), University of Minho, Campus of Gualtar, Braga, Portugal ICVS/3B's - PT Government Associate Laboratory, Braga, Guimarães, Portugal IPATIMUP - Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal Medical Faculty, University of Porto, Porto, Portugal Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Canada Department of Pathology, University Health Network, Toronto, Canada Barretos School of Health Sciences, Dr. Paulo Prata - FACISB, Barretos, Sao Paulo, Brazil.
authors.forename: Filipa
authors.initials: F
authors.lastname: Morais-Santos
authors.forename: Vera
authors.initials: V
authors.lastname: Miranda-Gonçalves
authors.forename: Sílvia
authors.initials: S
authors.lastname: Pinheiro
authors.forename: André F
authors.initials: AF
authors.lastname: Vieira
authors.forename: Joana
authors.initials: J
authors.lastname: Paredes
authors.forename: Fernando C
authors.initials: FC
authors.lastname: Schmitt
authors.forename: Fátima
authors.initials: F
authors.lastname: Baltazar
authors.forename: Céline
authors.initials: C
authors.lastname: Pinheiro
mesh_terms: D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003373:Coumaric Acids / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007191:Indazoles / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D027501:Monocarboxylic Acid Transporters / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D014162:Transfection
chemical_list: D003373:Coumaric Acids; D007191:Indazoles; D027501:Monocarboxylic Acid Transporters; D034741:RNA, Small Interfering; C007175:alpha-cyano-4-hydroxycinnamate; D011794:Quercetin; C016371:lonidamine
keywords: breast; carcinoma; molecular biology