Annasofia Anemone1, Lorena Consolino1, Laura Conti2, Pietro Irrera3, Myriam Y Hsu1, Daisy Villano1, Walter Dastrù1, Paolo E Porporato2, Federica Cavallo2, Dario Livio Longo4. 1. Department of Molecular Biotechnology and Health Sciences, Molecular Imaging Center, University of Torino, Via Nizza 52, Torino, Italy. 2. Department of Molecular Biotechnology and Health Sciences, University of Torino, Via Nizza 52, Torino, Italy. 3. University of Campania "Luigi Vanvitelli", Viale Abramo Lincoln, 5, Caserta, Italy. 4. Institute of Biostructures and Bioimaging (IBB), Italian National Research Council (CNR), Via Nizza 52, Torino, Italy. dariolivio.longo@cnr.it.
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: The higher metastatic potential of 4T1 and TS/A primary tumours, in comparison to the less aggressive TUBO and BALB-neuT ones, was confirmed by the highest expression of cancer cell stem markers (CD44+CD24-), 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.
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. Murinetumour 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: The higher metastatic potential of 4T1 and TS/A primary tumours, in comparison to the less aggressive TUBO and BALB-neuT ones, was confirmed by the highest expression of cancer cell stem markers (CD44+CD24-), 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.
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