Tumour acidosis evaluated in vivo by MRI-CEST pH imaging reveals breast cancer metastatic potential
Annasofia Anemone, Lorena Consolino, Laura Conti, Pietro Irrera, Myriam Y. Hsu, Daisy Villano, Walter Dastrù, Paolo E. Porporato, Federica Cavallo, Dario Livio Longo
Abstract
BACKGROUND: Tumour acidosis is considered to play a central role in promoting cancer invasion and migration, but few studies have investigated in vivo how tumour pH correlates with cancer invasion. This study aims to determine in vivo whether tumour acidity is associated with cancer metastatic potential. METHODS: Breast cancer cell lines with different metastatic potentials have been characterised for several markers of aggressiveness and invasiveness. Murine tumour models have been developed and assessed for lung metastases and tumour acidosis has been assessed in vivo by a magnetic resonance imaging-based chemical exchange saturation transfer (CEST) pH imaging approach. RESULTS: ), highlighting their propensity to migrate and invade, coinciding with the measurement obtained by in vitro assays. MRI-CEST pH imaging successfully discriminated the more aggressive 4T1 and TS/A tumours that displayed a more acidic pH. Moreover, the observed higher tumour acidity was significantly correlated with an increased number of lung metastases. CONCLUSIONS: The findings of this study indicate that the extracellular acidification is associated with the metastatic potential.