Targeting lactate transport suppresses in vivo breast tumour growth

• Type: Article in International Scientific Journal
• Date: 2015

Authors

Morais Santos, F (Author) Other; Granja, S (Author) Other; Miranda Goncalves, V (Author) Other; Moreira, AHJ (Author) Other; Queiros, S (Author) Other; Vilaca, JL (Author) Other; Fernando Schmitt (Author) FMUP; Longatto Filho, A (Author) Other; Paredes, J (Author) Other; Baltazar, F (Author) Other; Pinheiro, C (Author) Other

Journal

Title: Oncotarget

Vol. 6

ISSN: 1949-2553

Publisher: Impact Journals

Indexing

ISI Web of Knowledge - 82 Citations

Scopus - 82 Citations

Other information

Authenticus ID: P-00G-F8S

Abstract (EN): Background: Most cancers, including breast cancer, have high rates of glucose consumption, associated with lactate production, a process referred as "Warburg effect". Acidification of the tumour microenvironment by lactate extrusion, performed by lactate transporters (MCTs), is associated with higher cell proliferation, migration, invasion, angiogenesis and increased cell survival. Previously, we have described MCT1 up-regulation in breast carcinoma samples and demonstrated the importance of in vitro MCT inhibition. In this study, we performed siRNA knockdown of MCT1 and MCT4 in basal-like breast cancer cells in both normoxia and hypoxia conditions to validate the potential of lactate transport inhibition in breast cancer treatment. Results: The effect of MCT knockdown was evaluated on lactate efflux, proliferation, cell biomass, migration and invasion and induction of tumour xenografts in nude mice. MCT knockdown led to a decrease in in vitro tumour cell aggressiveness, with decreased lactate transport, cell proliferation, migration and invasion and, importantly, to an inhibition of in vivo tumour formation and growth. Conclusions: This work supports MCTs as promising targets in cancer therapy, demonstrates the contribution of MCTs to cancer cell aggressiveness and, more importantly, shows, for the first time, the disruption of in vivo breast tumour growth by targeting lactate transport.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 13