MDA-MB-231 breast cancer cells fuel osteoclast metabolism and activity: A new rationale for the pathogenesis of osteolytic bone metastases

Publication date: Available online 1 September 2017 Source:Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease Author(s): Silvia Lemma, Gemma Di Pompo, Paolo E. Porporato, Martina Sboarina, Shonagh Russell, Robert J. Gillies, Nicola Baldini, Pierre Sonveaux, Sofia Avnet Recent progress in dissecting the molecular paracrine circuits of cancer and stromal cells in bone metastases (BM) are offering new options to improve current merely palliative approach. The study of tumor-stroma metabolic interplay may further ameliorate this scenario. In this context, we demonstrated that highly glycolytic MDA-MB-231 cancer cells, that form osteolytic BM in vivo, release a large amount of lactate at a significantly higher level than MCF7 cells. Thus, we speculated that lactate released from carcinoma cells is uptaken and metabolically used by osteoclasts, the key players of osteolysis associated with BM. First, we demonstrated that the release of lactate at the bone site is mediated by monocarboxylate transporter 4 (MCT4), as revealed by immunostaining and MCT4 localization at the plasma membrane of tumor cells in mouse model of BM and in human tissue sections of BM. Then, we showed that in vitro lactate is uptaken by osteoclasts to be used as a fuel for the oxidative metabolism of osteoclasts, ultimately enhancing Type I collagen resorption. The passive transport of lactate into osteoclasts was mediated by MCT1: MCT1 expression is significantly upregulated during ost...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research